I do not know about Fallout 3, but typically games you can mod look for the mods somewhere other than the installation directory which could be why SecuROM does not cause issues with mods for them. If that is the case then we would just need a way to tell the game to look elsewhere when loading stuff.
I'm mostly familiar with Bethesda's games when it comes to modding, but in all cases the mods go into the main installation directory. Which can be a bit of a menace if one doesn't keep track of one's own changes, but that's how it is.
On the other hand, looking at the likes of Sims, the mods tend to go into the user's own documents/settings/whatever directory, so I guess it depends on the implementation. I don't think it's related to the type of DRM, though. At least that's not something I've heard, which admittedly could mean something else entirely...