diff --git a/CHANGES.md b/CHANGES.md
index cbb594129..d4673412d 100644
--- a/CHANGES.md
+++ b/CHANGES.md
@@ -1,5 +1,11 @@
 # Release Notes
 
+## 2.33.8
+
+This release makes running a PEX using venv-execution and sh-bootstrapping (that is, build with `--sh-boot --venv`) more likely to behave identically with a cold or warm `PEX_ROOT` cache. This includes running with `PEX_PYTHON=...`,  `PEX_PYTHON_PATH=...`, `PEX_PATH=...`, `PEX_VENV=...` and `PEX_IGNORE_RCFILES=...`.
+
+* Avoid fast-path in `--sh-boot` script for more variables. (#2729)
+
 ## 2.33.7
 
 This release fixes `PEX_TOOLS=1 ./path/to/pex` for PEXes using venv-execution and sh-bootstrapping (that is, built with `--sh-boot --venv=... --include-tools` ). Previously, the `PEX_TOOLS=1` was ignored if the venv already existed in the `PEX_ROOT` (for instance, if the PEX had already been run).
@@ -222,7 +228,7 @@ In addition, the 2.24.2 release included a wheel with no compression
 This release fixes a long-standing bug in "YOLO-mode" foreign platform
 speculative wheel builds. Previously if the speculatively built wheel
 had tags that did not match the foreign platform, the process errored
-pre-emptively. This was correct for complete foreign platforms, where 
+pre-emptively. This was correct for complete foreign platforms, where
 all tag information is known, but not for all cases of abbreviated
 platforms, where the failure was overly aggressive in some cases. Now
 foreign abbreviated platform speculative builds are only rejected when
diff --git a/pex/sh_boot.py b/pex/sh_boot.py
index 50ab689e6..5783bf7f7 100644
--- a/pex/sh_boot.py
+++ b/pex/sh_boot.py
@@ -181,6 +181,43 @@ def create_sh_boot_script(
             pex_info.raw_pex_root, pex_hash, expand_pex_root=False
         )
 
+    # There's a fast-path that execs the entrypoint directly within a venv if one exists (i.e. the
+    # PEX_ROOT cache is warm), but it is only possible in cases where we can be reasonably sure:
+    #
+    # - the venv is configured correctly for the current execution (if not, executing with a cold
+    #   cache may behave differently)
+    # - we do not need to execute any pex code (the venv has no such code)
+    #
+    # NB. we do not consider the contents of rc files, which can set any of these options.
+    #
+    # This should be kept in sync with env vars read (or not) by the venv_pex.py code, for which
+    # warnings are silenced.
+    vars_for_no_fast_path = [
+        # This is used when loading ENV (Variables()):
+        "PEX_IGNORE_RCFILES",
+        # And ENV is used to control the venv (e.g. whether to use a venv at all, which Python
+        # interpreter, any extra PEXes to include):
+        "PEX_VENV",
+        # (Determining the correct path when these are set would require reproducing (in highly
+        # portable shell) the hashing logic from `venv_dir` in `pex.variables`.)
+        "PEX_PYTHON",
+        "PEX_PYTHON_PATH",
+        "PEX_PATH",
+        # PEX_TOOLS requires executing PEX code, but the in-venv code is PEX-free and doesn't inspect
+        # `PEX_TOOLS=1`.
+        #
+        # (NB. unlike the ones above, this doesn't influence the venv contents.)
+        "PEX_TOOLS",
+        # Other variables that are used during bootstrap / not read by venv_pex.py, but don't result
+        # in behaviour differences between a cold or warm cache:
+        #
+        # "PEX_ROOT",
+        # "PEX_VERBOSE",
+        # "PEX_EMIT_WARNINGS",
+        # "PEX_MAX_INSTALL_JOBS",
+        # "PEX_DISABLE_VARIABLES",
+    ]
+
     return dedent(
         """\
         # N.B.: This script should stick to syntax defined for POSIX `sh` and avoid non-builtins.
@@ -199,11 +236,11 @@ def create_sh_boot_script(
         PEX_ROOT="${{PEX_ROOT:-${{DEFAULT_PEX_ROOT}}}}"
         INSTALLED_PEX="${{PEX_ROOT}}/{pex_installed_relpath}"
 
-        if [ -n "${{VENV}}" -a -x "${{INSTALLED_PEX}}" -a -z "${{PEX_TOOLS:-}}" ]; then
+        if [ -n "${{VENV}}" -a -x "${{INSTALLED_PEX}}" -a {check_no_fast_path} ]; then
             # We're a --venv execution mode PEX installed under the PEX_ROOT and the venv
             # interpreter to use is embedded in the shebang of our venv pex script; so just
-            # execute that script directly... except if we're needing to execute PEX code, in
-            # the form of the tools.
+            # execute that script directly... except if we're executing in a non-default manner,
+            # where we'll likely need to execute PEX code.
             export PEX="{pex}"
             exec "${{INSTALLED_PEX}}/bin/python" ${{VENV_PYTHON_ARGS}} "${{INSTALLED_PEX}}" \\
                 "$@"
@@ -267,4 +304,5 @@ def create_sh_boot_script(
             shlex_quote(venv_python_arg) for venv_python_arg in venv_python_args
         ),
         pex="$0" if layout is Layout.ZIPAPP else '$(dirname "$0")',
+        check_no_fast_path=" -a ".join(" -z {}".format(name) for name in vars_for_no_fast_path),
     )
diff --git a/pex/variables.py b/pex/variables.py
index dd536abf4..c9f5fa8de 100644
--- a/pex/variables.py
+++ b/pex/variables.py
@@ -834,7 +834,8 @@ def venv_dir(
 
     # The venv contents are affected by which PEX files are in play as well as which interpreter
     # is selected. The former is influenced via PEX_PATH and the latter is influenced by interpreter
-    # constraints, PEX_PYTHON and PEX_PYTHON_PATH.
+    # constraints, PEX_PYTHON and PEX_PYTHON_PATH. (NB. `create_sh_boot_script` in `pex.sh_boot`
+    # has code to disable its fast-path that must be kept in sync with the logic here.)
 
     pex_path_contents = {}  # type: Dict[str, Dict[str, str]]
     venv_contents = {"pex_path": pex_path_contents}  # type: Dict[str, Any]
diff --git a/pex/version.py b/pex/version.py
index 232a3aa7c..2f370edbc 100644
--- a/pex/version.py
+++ b/pex/version.py
@@ -1,4 +1,4 @@
 # Copyright 2015 Pex project contributors.
 # Licensed under the Apache License, Version 2.0 (see LICENSE).
 
-__version__ = "2.33.7"
+__version__ = "2.33.8"
diff --git a/tests/integration/test_sh_boot.py b/tests/integration/test_sh_boot.py
index 3b381afae..ecd431fb7 100644
--- a/tests/integration/test_sh_boot.py
+++ b/tests/integration/test_sh_boot.py
@@ -345,3 +345,61 @@ def _check_pex_tools():
 
     # run the tools with seeded PEX_ROOT
     _check_pex_tools()
+
+
+@execution_mode
+def test_issue_2728_pex_python_and_pex_python_path(
+    tmpdir,  # type: Any
+    execution_mode_args,  # type: List[str]
+):
+    # type: (...) -> None
+    pex = os.path.realpath(os.path.join(str(tmpdir), "pex.sh"))
+
+    run_pex_command(args=["-o", pex] + execution_mode_args).assert_success()
+    pex_root = os.path.join(str(tmpdir), "pex_root")
+
+    def _check_pex_with_python():
+        for env in [dict(PEX_PYTHON="FIXME"), dict(PEX_PYTHON_PATH="FIXME")]:
+            output = subprocess.check_output(
+                args=[pex, "-c", "import sys; print(sys.version)"],
+                env=make_env(PEX_ROOT=pex_root, **env),
+                stderr=subprocess.STDOUT,
+            )
+            assert False, "FIXME"
+
+    _check_pex_with_python()
+
+    # ensure the PEX_ROOT is fully seeded e.g. with a venv for venv execution mode
+    subprocess.check_output(args=[pex, "-c", ""], env=make_env(PEX_ROOT=pex_root))
+
+    _check_pex_with_python()
+
+
+@execution_mode
+def test_issue_2728_pex_path(
+    tmpdir,  # type: Any
+    execution_mode_args,  # type: List[str]
+):
+    # type: (...) -> None
+    pex = os.path.realpath(os.path.join(str(tmpdir), "pex.sh"))
+
+    run_pex_command(args=["-o", pex] + execution_mode_args).assert_success()
+    pex_root = os.path.join(str(tmpdir), "pex_root")
+
+    cowsay = os.path.join(str(tmpdir), "cowsay.pex")
+    run_pex_command(args=["cowsay==4.0", "-o", cowsay]).assert_success()
+
+    def _check_pex_with_path():
+        output = subprocess.check_output(
+            args=[pex, "-c", "import cowsay; print(cowsay.__version__)"],
+            env=make_env(PEX_ROOT=pex_root, PEX_PATH=cowsay),
+            stderr=subprocess.STDOUT,
+        )
+        assert b"4.0\n" == output
+
+    _check_pex_with_path()
+
+    # ensure the PEX_ROOT is fully seeded e.g. with a venv for venv execution mode
+    subprocess.check_output(args=[pex, "-c", ""], env=make_env(PEX_ROOT=pex_root))
+
+    _check_pex_with_path()