diff --git a/changelog/6213.improvement.rst b/changelog/6213.improvement.rst
new file mode 100644
index 000000000..735d4455f
--- /dev/null
+++ b/changelog/6213.improvement.rst
@@ -0,0 +1 @@
+pytester: the ``testdir`` fixture respects environment settings from the ``monkeypatch`` fixture for inner runs.
diff --git a/src/_pytest/pytester.py b/src/_pytest/pytester.py
index f44a69a95..97ad953a3 100644
--- a/src/_pytest/pytester.py
+++ b/src/_pytest/pytester.py
@@ -547,7 +547,8 @@ class Testdir:
 
         # Environment (updates) for inner runs.
         tmphome = str(self.tmpdir)
-        self._env_run_update = {"HOME": tmphome, "USERPROFILE": tmphome}
+        mp.setenv("HOME", tmphome)
+        mp.setenv("USERPROFILE", tmphome)
 
     def __repr__(self):
         return "<Testdir {!r}>".format(self.tmpdir)
@@ -853,12 +854,6 @@ class Testdir:
         plugins = list(plugins)
         finalizers = []
         try:
-            # Do not load user config (during runs only).
-            mp_run = MonkeyPatch()
-            for k, v in self._env_run_update.items():
-                mp_run.setenv(k, v)
-            finalizers.append(mp_run.undo)
-
             # Any sys.module or sys.path changes done while running pytest
             # inline should be reverted after the test run completes to avoid
             # clashing with later inline tests run within the same pytest test,
@@ -1091,7 +1086,6 @@ class Testdir:
         env["PYTHONPATH"] = os.pathsep.join(
             filter(None, [os.getcwd(), env.get("PYTHONPATH", "")])
         )
-        env.update(self._env_run_update)
         kw["env"] = env
 
         if stdin is Testdir.CLOSE_STDIN:
@@ -1261,11 +1255,7 @@ class Testdir:
             pytest.skip("pexpect.spawn not available")
         logfile = self.tmpdir.join("spawn.out").open("wb")
 
-        # Do not load user config.
-        env = os.environ.copy()
-        env.update(self._env_run_update)
-
-        child = pexpect.spawn(cmd, logfile=logfile, env=env)
+        child = pexpect.spawn(cmd, logfile=logfile)
         self.request.addfinalizer(logfile.close)
         child.timeout = expect_timeout
         return child
diff --git a/testing/test_pdb.py b/testing/test_pdb.py
index 25d2292e9..0f7816dbe 100644
--- a/testing/test_pdb.py
+++ b/testing/test_pdb.py
@@ -22,7 +22,7 @@ def pdb_env(request):
     if "testdir" in request.fixturenames:
         # Disable pdb++ with inner tests.
         testdir = request.getfixturevalue("testdir")
-        testdir._env_run_update["PDBPP_HIJACK_PDB"] = "0"
+        testdir.monkeypatch.setenv("PDBPP_HIJACK_PDB", "0")
 
 
 def runpdb_and_get_report(testdir, source):
diff --git a/testing/test_pytester.py b/testing/test_pytester.py
index 5bdbacdd0..3dab13b4b 100644
--- a/testing/test_pytester.py
+++ b/testing/test_pytester.py
@@ -550,17 +550,15 @@ def test_no_matching_after_match():
     assert str(e.value).splitlines() == ["fnmatch: '*'", "   with: '1'"]
 
 
-def test_pytester_addopts(request, monkeypatch):
+def test_pytester_addopts_before_testdir(request, monkeypatch):
+    orig = os.environ.get("PYTEST_ADDOPTS", None)
     monkeypatch.setenv("PYTEST_ADDOPTS", "--orig-unused")
-
     testdir = request.getfixturevalue("testdir")
-
-    try:
-        assert "PYTEST_ADDOPTS" not in os.environ
-    finally:
-        testdir.finalize()
-
-    assert os.environ["PYTEST_ADDOPTS"] == "--orig-unused"
+    assert "PYTEST_ADDOPTS" not in os.environ
+    testdir.finalize()
+    assert os.environ.get("PYTEST_ADDOPTS") == "--orig-unused"
+    monkeypatch.undo()
+    assert os.environ.get("PYTEST_ADDOPTS") == orig
 
 
 def test_run_stdin(testdir):
@@ -640,14 +638,10 @@ def test_popen_default_stdin_stderr_and_stdin_None(testdir):
 
 
 def test_spawn_uses_tmphome(testdir):
-    import os
-
     tmphome = str(testdir.tmpdir)
+    assert os.environ.get("HOME") == tmphome
 
-    # Does use HOME only during run.
-    assert os.environ.get("HOME") != tmphome
-
-    testdir._env_run_update["CUSTOMENV"] = "42"
+    testdir.monkeypatch.setenv("CUSTOMENV", "42")
 
     p1 = testdir.makepyfile(
         """