Seeing as he's the main antagonist and appeared in every Resident Evil after Code Veronica (so far), I'm guessing yes. But there's no word on a Resident Evil 6. In fact, there's been talk on the whole series being rebooted.
After the Dark Chronicles, the series is suppose to "reboot" and have an entirely new director. Based on the amount of publicity Wesker had on the last Resident Evil, I'd say there is a good chance he will eventually return to Resident Evil.