It's well known that it can be hard to even run / start Fallout 3, for some more than others. The list of problems and possible solutions is long and I want to add something, which I haven't found anywhere else, that helped me launch the game.

Turns out, a GOG update itself was the problem. After trying many different things, I ended up downloading the offline installer from gog.com to install FO3. As soon as the installation was finished, GOG Galaxy detected the game, updated it, activated cloud sync etc. The game still did not launch. However, one time I directly launched the game after installation (via the offline installers) before gog galaxy could apply its automatic update - and the game launched (and runs) perfectly well so far. No admin rights required, no deleting .ini files, no mods, no windowed mode or turning off vsync, no compatibility mode etc. It just works now.

In case someone finds this who tried "everything" to make FO3 launch without success: Just turn off auto-update in gog galaxy (for just FO3 or in general), just take care that no update is applied after installing it through the offline installers.

Just some of my specs: I run the game on a Win11 PC, Nvidia RTX 3080, AMD Ryzen 7 5800X, all drivers etc, are up-to-date

Hope this helps someone out there running this gem again!
Also, if anyone knows how this info can find its way up the chain in GOG to fix the update the galaxy launcher applies, this would be great!

best,
Marc