Polylith doesn't prescribe or restrict anything, here. I myself use environment variables (for my deployed projects), in conjunction with integrant and aero which together allow me to specify #env SOME_ENV_NAME in my integrant configs. Seems environ works similarly though it appears more geared to lein and boot, as well as simple env variables. Polylith projects use deps.edn instead, so you'll have to make do with environment variables. Set them then launch your REPL before connecting to it, rather than launching the REPL from cider or calva with the jack-in command.

I was unaware of aero. I like its design better then environ and will be using it. Thank you!

Sure, no prob! Also a small clarification on my setup: I have quite a few system.edn files.. the one in development/resources is the one that is read when I work at the REPL, using functions in development/src/user.clj This one does not make use of env variables (anymore), as this system.edn file is not checked into git anyway. When I first started I would have env vars in there but got annoyed at having to set them up before launching my REPL. The project-specific system.edn files however do make use of env vars, as I explained above.