I'm kind of surprised to hear that was a concern because my perception is that PyO3 is more analogous to wrapping native C code in Python libraries (which is pretty well established since long before either Rust or WASM), and Pyodide seems more like something for use in browsers rather on the server-side. When I looked into this earlier this year, trying to run Python via WASM on the server side with Pyodide had a bunch of hoops I needed to jump through, and it ended up being a lot simpler to use a build of Python from one of the core Python contributors that directly targeted WASM.

It won't work in those cases. Do you have explicit examples? I suspect this won't come up much as Rust has, IME, much broader target support. (Including platforms without a GPOS)

For the same reasons someone might prefer Rust to C in general; safety, ergonomics, etc. If you want to write C in Python, nothing is stopping you.

You can do that too. I generally prefer rust as it's a nice lang to work with.