Didn't he make an appearance in Code Veronica? I read up on a history faq and it says that he escaped with severe injuries after his battle with Chris Redfield. But even though RE4 is a sidestory, it just means that the events in that game are taking place after the Raccoon City incident. 6 years is enough time for Wesker to hide in the shadows and continue plotting against his enemies.
When the tyrant "Killed" him at the end of RE1 he had already injected himself with a virus much like the G-virus that would revive him with super human strength. The plan was with his new strength he could get data on the tyrant and take it to a rival company where he could become one of their big players. He was responsible for Ada's role in RE2 and was in CVX with the new company after the T-Veronica and T-Alexia viruses. And was behind the scenes in RE4
You wouldn't really know that unless you played previous RE games. I read more about the series after completing RE4. He's considered to be the main villain by many. There are a couple of documentaries that came with Code Veronica (I think) called Wesker's Files and they're essentially narratives by him explaining what he was doing throughout the series and what his intentions were.