According to an interview with 3D Realm's Scott Miller at Next-Gen, his team is already hard at work on Prey 2.
In Prey, players enter a monstrous spaceship designed for enslaving and devouring humans. A unique twist on the first person shooter genre, Prey features such innovations as the ability to walk on walls, manipulate gravity and perform a "spirit walk" by leaving your physical body behind. Designed by Human Head and brought to Xbox 360 by Venom Games (under the direction of 3D Realms), Prey features full online support for up to eight players, utilizing the game's play innovations for unique multiplayer experiences.
In the interview Miller responded to a question regarding his current project by saying, "Prey 2, of course! We are addressing concerns about combat, as well as adding in more gameplay innovations."
A representative from 3D realms was not available for comment.