The Seriously! Forums (thanks Frans) feature a bit of translation from a print interview with Croteam that reveals a bit about plans for the next installment in the Serious Sam series, though they warn that this is subject to change based on the potential that all long-terms plans have at shifting as well as the possibility that they have made errors in translating. Here's word that also covers a more "serious" game:

First we have to finish the patches (DM, SDK, linux port etc. - as they mentioned in another part of the interview, G.), then adapt SS 2 for other platforms, and then start working on SS 3 (!!!, G.)... Of course, you never know what the publisher may want, so something may happen in between. We are also planning a completely new project, a game which will be completely different from SS, with a bigger accent on MP in co-op... It should be a lot less "cartoony" and much more serious than Sam. But don't worry, it won't be too serious - can you even imagine the two of us making a really serious game (Alen and Vedran, G.) ?!