Cool, you’re right that Pants is able to find an interp to run Pex with. There are two different context we look for an interpreter: 1. what to run the Pex CLI tool with, which can be any valid 2.7 or 3.5+ interp 2. what to use for your own code, which we delegate to Pex because it understands things like interpreter constraints #1 is working as we’d expect, but #2 is not for some reason. That error message you’re getting is coming from Pex. And it looks like Pants is properly setting everything for Pex, so I suspect there could be an issue with Pex itself