Following the fall of Umbrella, Wesker soon proved to be a problem for his Organization superiors. Wesker had always cherished a desire for power, prominence and domination over others, and, seeing Umbrella as power incarnate, used it to hide behind while he made plans of his own. He established a secret organization of his own, using Umbrella's infrastructure retrieved from the Umbrella Caucasus Research Facility, and began recruiting agents such as Jack Krauser into it. When Umbrella folded, and the sanctuary and protection it provided ruined by the surviving Umbrella leaders' constant power struggles, Wesker decided that bringing his new Umbrella to complete fruition was his most necessary goal. He would need to amass much wealth and resources. In order to achieve this, Wesker planned to go down the list of Umbrella's other top rival corporations, sell them samples of Umbrella's viruses they desired, and finance his personal empire. He would keep this agenda secret from his Organization superiors, though they were suspicious.
Wesker began his plot with Tricell (disguised with the name "S"), who had been interested in acquiring a sample of the newly discovered Las Plagas parasitic organism, preferably an advanced Control Plaga developed by Los Illuminados cult leader, Osmund Saddler. Wesker contacted Tricell and struck the deal. He commissioned Ada Wong, his old partner, to once again aid the field portion of the operation, while Wesker himself remained at his hideout and kept in touch with her via digital video feed. All the while, he contacted her for reports and updates in the objective. Wesker was apparently on a deadline to retrieve the sample, and made it his and Ada's most important goal. He also sent Krauser in to help Ada, though they were at conflict. Krauser thought that Ada would betray Wesker and said that neither of them trusted her, and Ada noted in her report that she wondered if Wesker had sent her to keep an eye on Krauser. Nothing suggests which of the two Wesker trusted more, though he considered them both expendable pawns.
Wesker gave Ada assignments to deal with people in the area, including Luis Sera and Leon S. Kennedy. Luis was a contact of theirs, and he was making attempts from inside the cult to steal the Control Plaga sample. Wesker made it important for Ada to watch over Luis, but he was soon killed by Saddler, and the retrieved sample was lost. Wesker was not concerned, simply saying "There will be another time...", and didn't pity Luis. Wesker also saw Leon as an extra obstacle and ordered Ada to kill him, though she insisted he was of no trouble. She was quite reluctant to carry out Wesker's order, as she had formed a bond with Leon in Raccoon City. When Wesker later asked if she had gotten a chance to kill him, she lied and said the opportunity had not come. Wesker decided to let Leon live for the time being and allowed him to serve as further distraction for Saddler's followers. He later informed Ada of the Illuminados' panic due to Leon's actions, and decided to have Krauser kill Leon instead. Ada saved him, not playing by Wesker's rules.
Ada falsely reported Krauser was dead to Wesker, who found it interesting how easily Leon could avoid death. This implies that Wesker was suspicious of Ada and quite aware that she had let Leon live, and that Krauser was alive as well. He decided to let Leon take care of Saddler himself, and told Ada to eliminate either one still standing when the fight ended. He reminded Ada that he was running the show, and required her to put a halt to whoever could stall their plans, including Leon. Krauser himself was later killed for real by Ada, who said that she didn't want to fill out a large amount of paper work should Krauser return alive. Ada later helped Leon destroy Saddler and stole the sample without killing him, though Wesker may have been aware of this. It was revealed that Ada was not at all loyal to Wesker, but still to the Organization, whom Wesker had gone against. She sent him a false Control Plaga sample on their orders (actually a Modified Subordinate Plaga), and brought them the real sample.
This, however, only stalled Wesker's plans temporarily. Tricell still compensated Wesker greatly for the different sample he provided, as they managed to put it to use. Wesker left the Organization shortly afterwards, apparently no longer needing them. Ever since his faked death, Wesker managed to hide himself in the shadows flawlessly, and it was no trouble for him to avoid his vengeful superiors.
