His issue is he made his fame on the Clerks-a-verse films, but when he tried to branch out from that (Red State, Tusk, Zack and Miri), they all fell pretty flat. His attempts to return to the Clerks-a-verse also fell flat, so it isn't surprising he doesn't have much pull for major films anymore. He still has the nerd niche thing going, which can net you a comfortable living.
I met him once in person. A girl I knew was obsessed with him and we went to a signing he was attending at the now defunct Words and Pictures museum. So she gets her turn in line and she has an ultra geek out meltdown and asks if she can squeeze his cheeks, which he declined in a pretty lol fashion (ie, fearful), but he let her pinch his belly or something. He actually did a ton of modifications to a Chasing Amy poster she gave him (it was some odd international version as well...it was in Italian or Spanish I think), then wrote that she should calm the fuck down on it lol.