Do you use executable mods? Downgraders, engine fixes, etc? I'm also curious what mod manager you use, because getting MO2 to work under linux is a bit janky as well.

Probably not often I'd say, but at least there were some games I played with wine where some executables to apply mods also ran in wine and worked, I vaguely remember some fix to make something be able to use more than a few GB of ram to allow farther or better remdering, sometimes just a strange combination of things is needed to get something to work. But that's actually long ago, these days everything just works in Steam instead

I use MO2 on Linux through Steam's Proton runtime, to play TTW (Fallout NV mod). Works fine. The TTW installer did require an older Proton version though.