User blog comment:CrimsonShogun/My opinion on the Future of Mass Effect/@comment-1786741-20120821120746

Eh, I don't think it's even possible to make a viable sequel without setting it quite a while after ME3. There's simply too many variables, especially if everyone is half robot or some bull, to account for without ignoring the choices from the third game. At most, I see some sort of prequel but even then the possibility is slim.