diff --git a/pandas/core/resample.py b/pandas/core/resample.py
index f84bedda8d00c..53ae4f1c419b4 100644
--- a/pandas/core/resample.py
+++ b/pandas/core/resample.py
@@ -2576,42 +2576,80 @@ def _get_time_bins(self, ax: DatetimeIndex):
             )
 
         if len(ax) == 0:
-            binner = labels = DatetimeIndex(
-                data=[], freq=self.freq, name=ax.name, dtype=ax.dtype
-            )
-            return binner, [], labels
+            empty = DatetimeIndex(data=[], freq=self.freq, name=ax.name, dtype=ax.dtype)
+            return empty, [], empty
 
-        first, last = _get_timestamp_range_edges(
-            ax.min(),
-            ax.max(),
-            self.freq,
-            unit=ax.unit,
-            closed=self.closed,
-            origin=self.origin,
-            offset=self.offset,
-        )
-        # GH #12037
-        # use first/last directly instead of call replace() on them
-        # because replace() will swallow the nanosecond part
-        # thus last bin maybe slightly before the end if the end contains
-        # nanosecond part and lead to `Values falls after last bin` error
-        # GH 25758: If DST lands at midnight (e.g. 'America/Havana'), user feedback
-        # has noted that ambiguous=True provides the most sensible result
-        binner = labels = date_range(
-            freq=self.freq,
-            start=first,
-            end=last,
-            tz=ax.tz,
-            name=ax.name,
-            ambiguous=True,
-            nonexistent="shift_forward",
-            unit=ax.unit,
-        )
+        if ax.tz is not None:
+            try:
+                first, last = _get_timestamp_range_edges(
+                    ax.min(),
+                    ax.max(),
+                    self.freq,
+                    unit=ax.unit,
+                    closed=self.closed,
+                    origin=self.origin,
+                    offset=self.offset,
+                )
+                binner = labels = date_range(
+                    freq=self.freq,
+                    start=first,
+                    end=last,
+                    tz=ax.tz,
+                    name=ax.name,
+                    ambiguous=True,
+                    nonexistent="shift_forward",
+                    unit=ax.unit,
+                )
+            except Exception as e:
+                if "nonexistent" not in str(e).lower():
+                    raise
+
+                ax_utc = ax.tz_convert("UTC")
+
+                first_utc, last_utc = _get_timestamp_range_edges(
+                    ax_utc.min(),
+                    ax_utc.max(),
+                    self.freq,
+                    unit=ax.unit,
+                    closed=self.closed,
+                    origin=self.origin,
+                    offset=self.offset,
+                )
+
+                binner_utc = date_range(
+                    start=first_utc,
+                    end=last_utc,
+                    freq=self.freq,
+                    tz="UTC",
+                    name=ax.name,
+                    unit=ax.unit,
+                )
+
+                binner = labels = binner_utc.tz_convert(ax.tz)
 
+        else:
+            first, last = _get_timestamp_range_edges(
+                ax.min(),
+                ax.max(),
+                self.freq,
+                unit=ax.unit,
+                closed=self.closed,
+                origin=self.origin,
+                offset=self.offset,
+            )
+            binner = labels = date_range(
+                freq=self.freq,
+                start=first,
+                end=last,
+                tz=ax.tz,
+                name=ax.name,
+                ambiguous=True,
+                nonexistent="shift_forward",
+                unit=ax.unit,
+            )
         ax_values = ax.asi8
         binner, bin_edges = self._adjust_bin_edges(binner, ax_values)
 
-        # general version, knowing nothing about relative frequencies
         bins = lib.generate_bins_dt64(
             ax_values, bin_edges, self.closed, hasnans=ax.hasnans
         )
@@ -2627,9 +2665,6 @@ def _get_time_bins(self, ax: DatetimeIndex):
             binner = binner.insert(0, NaT)
             labels = labels.insert(0, NaT)
 
-        # if we end up with more labels than bins
-        # adjust the labels
-        # GH4076
         if len(bins) < len(labels):
             labels = labels[: len(bins)]
 
diff --git a/pandas/tests/resample/test_dst_handling.py b/pandas/tests/resample/test_dst_handling.py
new file mode 100644
index 0000000000000..bc7d0100efab5
--- /dev/null
+++ b/pandas/tests/resample/test_dst_handling.py
@@ -0,0 +1,240 @@
+import numpy as np
+import pytest
+
+from pandas import (
+    DataFrame,
+    DatetimeIndex,
+)
+
+
+class TestResampleDSTAfricaCairo:
+    """DST transition tests for Africa/Cairo timezone."""
+
+    def test_resample_across_dst_transition(self):
+        df = DataFrame(
+            {"value": [1, 2]},
+            index=DatetimeIndex(
+                [
+                    "2024-04-26 01:00:00",
+                    "2024-04-27 00:00:00",
+                ]
+            ).tz_localize("Africa/Cairo", nonexistent="shift_forward"),
+        )
+
+        result = df.resample("D").mean()
+
+        assert len(result) == 2
+        assert isinstance(result.index, DatetimeIndex)
+        assert result.index.tz is not None
+        assert not result.isna().any().any()
+
+    def test_resample_before_dst_boundary(self):
+        df = DataFrame(
+            {"value": [76.0, 42.0]},
+            index=DatetimeIndex(
+                [
+                    "2024-04-24 00:00:00",
+                    "2024-04-25 00:00:00",
+                ]
+            ).tz_localize("Africa/Cairo"),
+        )
+
+        result = df.resample("D").mean()
+
+        assert len(result) == 2
+        assert isinstance(result.index, DatetimeIndex)
+        assert "Africa/Cairo" in str(result.index.tz)
+        assert result.iloc[0, 0] == 76.0
+        assert result.iloc[1, 0] == 42.0
+
+    @pytest.mark.parametrize("freq", ["2h", "6h", "12h"])
+    def test_resample_various_freq(self, freq):
+        df = DataFrame(
+            {"value": [1, 2, 3, 4, 5]},
+            index=DatetimeIndex(
+                [
+                    "2024-04-25 22:00:00",
+                    "2024-04-25 23:00:00",
+                    "2024-04-26 01:00:00",
+                    "2024-04-26 02:00:00",
+                    "2024-04-26 03:00:00",
+                ]
+            ).tz_localize("Africa/Cairo", nonexistent="shift_forward"),
+        )
+
+        result = df.resample(freq).mean()
+
+        assert isinstance(result, DataFrame)
+        assert len(result) > 0
+        assert not result.isna().all().any()
+
+    def test_resample_closed_label_combinations(self):
+        df = DataFrame(
+            {"value": [1, 2]},
+            index=DatetimeIndex(
+                [
+                    "2024-04-26 01:00:00",
+                    "2024-04-27 00:00:00",
+                ]
+            ).tz_localize("Africa/Cairo", nonexistent="shift_forward"),
+        )
+
+        for closed in ["left", "right"]:
+            for label in ["left", "right"]:
+                result = df.resample("D", closed=closed, label=label).mean()
+                assert len(result) >= 1
+                assert not result.isna().all().any()
+
+    def test_resample_nonexistent_times(self):
+        timestamps = [
+            "2024-04-25 23:00:00",
+            "2024-04-26 00:30:00",
+            "2024-04-26 01:00:00",
+        ]
+
+        df = DataFrame(
+            {"value": [1, 2, 3]},
+            index=DatetimeIndex(timestamps).tz_localize(
+                "Africa/Cairo", nonexistent="shift_forward"
+            ),
+        )
+
+        result = df.resample("h").mean()
+
+        assert len(result) > 0
+        assert isinstance(result, DataFrame)
+
+    def test_resample_empty_dataframe(self):
+        df = DataFrame({"value": []}, index=DatetimeIndex([], tz="Africa/Cairo"))
+
+        result = df.resample("D").mean()
+
+        assert len(result) == 0
+        assert isinstance(result.index, DatetimeIndex)
+
+    def test_resample_single_point(self):
+        df = DataFrame(
+            {"value": [42.0]},
+            index=DatetimeIndex(["2024-04-26 12:00:00"]).tz_localize(
+                "Africa/Cairo", nonexistent="shift_forward"
+            ),
+        )
+
+        result = df.resample("D").mean()
+
+        assert len(result) == 1
+        assert result.iloc[0, 0] == 42.0
+
+
+class TestResampleDSTMultipleTimezones:
+    """DST handling across multiple timezones."""
+
+    def test_resample_multiple_timezones(self):
+        timezones = [
+            ("Africa/Cairo", "2024-04-26 01:00:00", "2024-04-27 00:00:00"),
+            ("Europe/London", "2024-03-31 01:00:00", "2024-04-01 00:00:00"),
+            ("America/New_York", "2024-03-10 01:00:00", "2024-03-11 00:00:00"),
+        ]
+
+        for tz, start, end in timezones:
+            df = DataFrame(
+                {"value": [1, 2]},
+                index=DatetimeIndex([start, end]).tz_localize(
+                    tz, nonexistent="shift_forward", ambiguous=True
+                ),
+            )
+
+            result = df.resample("D").mean()
+
+            assert len(result) >= 1
+            assert isinstance(result.index, DatetimeIndex)
+            assert result.index.tz is not None
+
+
+class TestResampleDSTEdgeCases:
+    """Edge cases around DST transitions."""
+
+    def test_resample_multiple_dst_days(self):
+        df = DataFrame(
+            {"value": [1, 2, 3, 4]},
+            index=DatetimeIndex(
+                [
+                    "2024-04-25 23:00:00",
+                    "2024-04-26 01:00:00",
+                    "2024-04-27 00:00:00",
+                    "2024-04-28 00:00:00",
+                ]
+            ).tz_localize("Africa/Cairo", nonexistent="shift_forward"),
+        )
+
+        result = df.resample("D").mean()
+
+        assert len(result) >= 3
+
+    def test_resample_microsecond_precision(self):
+        df = DataFrame(
+            {"value": [1.1, 2.2]},
+            index=DatetimeIndex(
+                [
+                    "2024-04-26 01:00:00.123456",
+                    "2024-04-27 00:00:00.654321",
+                ]
+            ).tz_localize("Africa/Cairo", nonexistent="shift_forward"),
+        )
+
+        result = df.resample("D").mean()
+
+        assert len(result) == 2
+
+    def test_resample_with_na_values(self):
+        df = DataFrame(
+            {"value": [1.0, np.nan, 3.0]},
+            index=DatetimeIndex(
+                [
+                    "2024-04-25 23:00:00",
+                    "2024-04-26 01:00:00",
+                    "2024-04-26 02:00:00",
+                ]
+            ).tz_localize("Africa/Cairo", nonexistent="shift_forward"),
+        )
+
+        result = df.resample("h").mean()
+
+        assert len(result) > 0
+        assert isinstance(result, DataFrame)
+
+
+class TestResampleDSTOriginalIssues:
+    """Tests reproducing the originally reported issues."""
+
+    def test_original_issue_1(self):
+        df = DataFrame(
+            {"value": [1, 2]},
+            index=DatetimeIndex(
+                [
+                    "2024-04-26 01:00:00",
+                    "2024-04-27 00:00:00",
+                ]
+            ).tz_localize("Africa/Cairo", nonexistent="shift_forward"),
+        )
+
+        result = df.resample("D").mean()
+
+        assert len(result) > 0
+        assert not result.isna().any().any()
+
+    def test_original_issue_2(self):
+        df = DataFrame(
+            {"value": [76.0, 42.0]},
+            index=DatetimeIndex(
+                [
+                    "2024-04-24 00:00:00",
+                    "2024-04-25 00:00:00",
+                ]
+            ).tz_localize("Africa/Cairo"),
+        )
+
+        result = df.resample("D").mean()
+
+        assert len(result) > 0
+        assert not result.isna().any().any()