The story of Resident Evil is a long and complicated thing. Lots of characters drop in and out of the franchise, and lots of little revelations are constantly being added to the series mythos. There are tons of Resident Evil games and movies that are ambiguously canon and the universe is set up in a way to allow almost anything to be possible. However, uniting it all is a strong core cast of characters that rotate in and out between games. Whether the story focuses on Chris Redfield and Jill Valentine's battle against Wesker and Umbrella’s evil ambitions, or Ethan Winters’ struggle to survive in a warped environment, there are lots of moments where the heroes and villains shape a cheesy and potentially convoluted story into something charming.
But for every plot Resident Evil uses, another falls through the cracks. Games like Resident Evil 6 and the Revelations titles have done a good job of uniting the extended cast, but some opportunities don't always line up. Characters from Chris Redfield's story tend to not interact with characters from Leon Kennedy's story, and aside from a few interventions from Chris, Ethan Winters has been remarkably isolated in his games. Even among these major characters, two of the most important and popular characters in the series have never actually met face-to-face. Albert Wesker, the main villain of the series up to Resident Evil 5, and sometimes-protagonist Leon Kennedy have never spoken on screen, and that's rather odd.
Why Wesker Wasn't Interested in Leon
From the beginning, Albert Wesker was more interested in gaining personal power than the affairs of the world. He only really took notice of national incidents or political drama when they suited his purposes, which gradually became more grandiose over time. Wesker's quest to become the ultimate lifeform seemingly failed in the first game, but it turned out that Wesker had gotten lucky and managed to resurrect himself with new powers and an intact mind. The most optimized form of the T-virus wasn't enough for him, however, and he set out to research bio-weapons, viruses, and parasites over the next few games, before finally bringing his master plan to bear in Resident Evil 5.
Wesker was aware of Leon but didn't have any personal investment in the rookie cop-turned-secret agent's life. The unlockable Separate Ways campaign in Resident Evil 4 reveals that Wesker was behind Ada Wong and Krauser's appearance in the story. Wesker wanted a sample of the Las Plagas parasite, and its delivery to him by Ada ends up causing the outbreak at the beginning of Resident Evil 5. In the meantime, Wesker gives Ada orders to either avoid or kill Leon on sight, something that she stays out of the way to avoid doing. Wesker views Leon as an irritation and potentially useful distraction, but nothing more. Ultimately, Wesker dies at the end of Resident Evil 5 at the hands of Chris and Sheva, so he won't get to meet Leon in the future.
Why Leon was Too Busy to Meet Wesker
Meanwhile, rookie cop Leon Kennedy was busy just trying to survive. Leon was caught in the thick of Resident Evil 2’s Raccoon City incident and had to fight his way out. Along the way, he met Ada Wong for the first time, who was already working as Wesker’s field proxy to hide his survival from Umbrella and S.T.A.R.S. Wesker gets his hands on a small G-virus sample, and all of the characters involved in the incident simply move on. Leon busies himself with maneuvering to a better position against Umbrella, eventually ending up as a US federal agent. In RE4, Leon travels to a remote village to rescue the current president's daughter Ashley from a sinister cult, and he briefly encounters Ada again during this assignment. After that, Leon continued working as an agent for the American government and showed up again as one of the many protagonists of Resident Evil 6.
It's not clear if Leon even knew who Wesker was. The two didn't mean anything to each other, and Leon's work never made him a direct threat to Wesker’s plans for world domination. The closest thing to Leon and Wesker interacting is in the fifth live-action Resident Evil movie, Resident Evil: Retribution, where Leon is the leader of a mercenary group working for Wesker. Wesker was helping the protagonists during that movie, so the two never come into conflict or contact. The other closest time the two have appeared together would have to be in certain iterations of The Mercenaries where both Leon and Wesker are playable. It seems like a missed opportunity that these two never appear on screen together, if only because fans missed out on Leon's snarking at Wesker’s plans. Perhaps Wesker will return someday end get another chance at encountering Leon, but with Resident Evil 9 already being set up, that is a long way off.