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Pants

Can I create a pex file that does not run in a virtual environment?

what do you mean? you want it to see the system environment? see <https://docs.pex-tool.org/api/vars.html#PEX_INHERIT_PATH>

You can create a zipapp pex that doesn't splat itself out to a virtualenv on first run, but you may run into issues

a venv pex generally works better with weird wheels that expect a venv layout

Can you give more details on the use case?

See the following thread. <https://pantsbuild.slack.com/archives/C046T6T9U/p1706297386310739> for background.