In general, yes. Most of the difficulty is due to being on Linux and running games through the Proton/WINE compatibility layer, so there can be an extra layer of jank involved, but it’s very possible.
If modding consists of dropping files into the game directory, it will work almost exactly the same as in Windows. However, if some of those files replace the game’s DLLs, then whatever WINE runner you use might need to be told to use the DLLs in the game directory instead of its own.
If you need to use a mod manager, that situation is still not ideal - native Linux mod managers I know of are only the Nexus Mods app (very new, there’s some talk of it being integrated directly into the Heroic launcher) and Limo. Everything else, you’ll be running whatever bespoke Windows mod manager your game uses through Proton/WINE, probably with Steam Tinker Launch, possibly Lutris.
tl;dr There can be an extra layer of complexity over modding on Windows, but it’s otherwise comparable.
In general, Bazzite being immutable just means the core system isn’t modular to the end user to the degree that Arch is. You of course can use flatpaks or appimages like any distro, and there are still several ways to install traditional rpm/deb/aur programs (the usual Fedora method doesn’t work because dnf doesn’t exist). If it’s just an app that doesn’t require significant integration with the OS, the recommendation is to install them into a distrobox container (where dnf does exist) and then
distrobox-export [program]
to make them visible to the host system. VPNs need a little more integration so those are installed by layering with rpm-ostree and then enabling the systemd service(s). Layering makes updates take longer to install so it should be avoided when possible.One of the interesting things about Universal Blue’s images like Bazzite is if you want the benefits of atomic while also having a more custom system than they offer without having to install a bunch of things in rpm-ostree, the process to build a custom image based on one of theirs is apparently quite easy to do and automate, though I haven’t done it myself.