Weskers New Organization

After months of hiding in the shadows, Wesker and the H.C.F. -a heavily armed assault force- attacked the Umbrella facility on Rockfort Island, intent on retrieving a sample of the T-Veronica virus by one of Umbrella's chief researchers Alexia Ashford. The t-virus was released in the process when armed conflict with Umbrella's guards took place.
The attack succeeded, especially when the t-virus samples and captive B.O.W's in the laboratory section of the facility broke containment and contaminated the Island. However, Wesker and his men failed to find the missing Alexia. Wesker then went to the Antarctic Research Facility, which had also suffered a t-virus outbreak from infected Rockfort employees fleeing to the facility.
It was here Wesker encountered his former subordinate Chris Redfield (who had arrived seeking his missing sister Claire). Wesker failed to gain a sample of the virus from Alexia, especially when he tried to use his own abilities to force her to surrender one, only to be driven back by Alexia's own abilities. Wesker then left Chris to fight Alexia, and secured a sample of the virus from the retrieved corpse of Steve Burnside. The base started its self-destruct sequence, but Wesker engaged Chris in combat, eager to settle the score. Wesker quickly used his immense strength and speed to gain dominance, with Chris refusing to allow Wesker an easy kill. Wesker was poised to deliver the finishing blow, only for an explosion, caused by the priming self-destruct, to knock a flaming pillar in between the two. Wesker, vowing Chris was lucky and next time they met he couldn't count on luck again, escaped the base as it began to crumble and explode around them. Wesker reached an Organization Submarine and sailed away. While the flaming pillar had badly burned Wesker's face, his burns healed sometime later due to his superhuman regenerative capabilities. It would be eight years later following this incident in which Wesker and Chris would meet each other for a confrontation once again.

Wesker,S.T.A.R.S,& Lisa Trevor

Wesker was not expecting Lisa's arrival, believing that S.T.A.R.S. had disposed of her in Jessica's tomb. He managed to incapacitate the creature, saying "Nobody's perfect, not even you, Lisa." He then went up in the elevator, heading back up to the mansion. However, after he left, Lisa rose up from the ground, still not dead. With what little of her mind was left, Lisa had no other goal but to take revenge on the man who experimented on and deformed her. She pursued Wesker up to the mansion, and approached him again in the main hall. Wesker noted that he needed to pick up his pace, as the 'hour glass' was running low. He resolved to find another route, not wishing to waste time with the stubborn Lisa, who he knew would pursue him tirelessly.

Fending off the remaining B.O.W.s, Wesker had several confrontations with Lisa, who continued to note as stubborn and at one point humorously saying "She must like me." He saw why she had been called immortal after all the weaponry he emptied into her and she still got up. Eventually, Lisa unexpectedly turned away from Wesker and walked away, and it seemed she had given up. However, when returning to the main hall, Wesker again saw her, this time hiding behind columns in a corner. She approached him one final time, and Wesker, tired of her stalking, said he would grant her wish for eternal rest. Using his new abilities, Wesker matched the persistence of Lisa, jumping high into the air to avoid her more damaging attacks.
Wesker shot the chandelier above them loose, and lured Lisa under it. She was crushed when it fell, and as Wesker walked out of the main hall, he said "Be a good girl and stay dead this time." He then quickly sprinted through the forest, trying to put as much distance as possible between himself and the mansion before it exploded. When it finally did, taking Lisa with it, Wesker looked back at the burning rubble triumphantly. The scenario served as a metaphorical representation of Wesker's proclaiming of being reborn "like a phoenix emerging from the flame." He saw a new horizon stretch out before him, and thought of how he had risen beyond the human race and "cheated death itself", leaving nothing to oppose him in his quest for power.

Wesker & Sergei

During the ensuing chaos, Wesker injected himself with an experimental virus given to him by his partner, William Birkin.^[14] After allowing the Tyrant to "kill" him, the virus reanimated his body after the room became empty. This gave him superhuman strength, agility and regeneration, but at the severe cost of the loss of his humanity. The resulting mutation also gave him gold-red cat-like eyes (but these were not immediately noticeable, due to the sunglasses he always wore). Wesker was revived, while the remaining S.T.A.R.S. operatives were convinced that the Tyrant killed him. After reviving, Wesker realized the S.T.A.R.S. had destroyed the Tyrant and escaped with their lives. He then tried to steal the data from the laboratory and escape.

Wesker found that Sergei had downloaded the data to the U.M.F-013 and the Red Queen had locked him from the mainframe system. He swore revenge against the remaining S.T.A.R.S. members, Sergei, and the Red Queen. His plans foiled, Wesker resolved to escape the mansion before the self-destruct timer ended. He was forced into a battle with the remaining B.O.W.s on his way to the exit, and praised his new immense powers when his enemies were swept away with little effort. Wesker mused that he hoped Chris and Jill would live long enough for the three of them to have their "tear-filled reunion", laughing evilly at the thought of seeing them again. He also had to deal with Lisa Trevor, who first approached Wesker outside an elevator leading to the surface from the lab.

The Mansion

By the following day, all contact with Bravo team was lost and Wesker's Alpha team was dispatched to the site.^[13] Upon arrival, Alpha team was attacked by a loose Cerberus pack^[13] and then, abandoned by their pilot, Brad Vickers.^[13] After the loss of member Joseph Frost to the dogs,^[13] Wesker and the remaining members of Alpha team sought refuge in the nearby mansion, where Wesker had previously worked.^[13] Initially ordering everyone to split up, Wesker disappeared and left the remaining members of Alpha team (Chris Redfield, Jill Valentine, and Barry Burton) to fend for themselves.^[13] Of the nine S.T.A.R.S. operatives who entered the mansion (including Wesker himself), only four members of Alpha team, along with Bravo team's Enrico Marini and Rebecca Chambers, managed to survive against the various creatures and bio-organic weapons that infested the facility. In order to ensure the downfall of the other members, Wesker used extortion in order to convince Barry to do his bidding (luring the others to traps) by threatening his family. When Enrico uncovered evidence that implicated Wesker and Umbrella, Wesker murdered Enrico.^[13] However, Chris and Jill learned the truth about Wesker and then proceeded to foil his plot by destroying the
T-002 Tyrant, along with the facility itself.