The plot revolves around Ada's search for Carla Radames and Derek C. Simmons. Moving in to China, she searches for any information on Carla's creation in order to destroy it, thereby wiping any data concerning her along with it.
Matchless in her ability and renowned in the underworld as a spy, Ada Wong one day receives an unexpected message. Presidential aide, Derek Simmons, apparently has some information he claims is of great interest to her future.
Curiosity piqued, Ada follows his instructions and infiltrates a submarine—which oddly has its security systems set to match her fingerprints. There, she finds orders from Simmons regarding the capture of Jake Muller, a young man who possessed antibodies to the C-Virus; however, the orders are from more than 6-months prior, and Ada has no recollection of having received them.
Ada wonders if someone else has carried out the orders in her place, or if Simmons was merely lying about the information.
Ada escapes the submarine, and receives another message from Simmons, this one informing her that the orders from six months ago are a large piece to the puzzle. Further, he reveals that Neo Umbrella will launch bioterror attacks first in America, then in China. Not wanting to be left out in the cold, Ada heads to America.
Good to his word, Simmons' bioterror attacks begin in Tall Oaks, where the president is infected and killed.
On her way to Simmons' laboratory, Ada runs into Leon and his partner Helena. Helena tells of how Simmons had kidnapped her sister Deborah and blackmailed Helena into cooperating in the Tall Oaks attack. Ada considers this story, and decides it wholly possible.
Simmons is afforded certain powers in his position as head of The Family, a generations-old shadow organization that manipulates global-scale politics in order to maintain international "stability"—meaning the continued wealth of The Family's members. After informing Leon and Helena of The Family's existence, Ada ventures further into the laboratory.
In the lab Ada finds a tape showing what appears to be herself being born from a cocoon.
For Ada, this solves one mystery: the person to whom Simmons had given the orders six months ago was not her, but her Neo-Umbrella doppelganger—a fake Ada. Furthermore, this fake Ada is now threatening the stability sought by The Family. Ada is unable to sit idle while this copy of her paraded about, and leaves to find and eliminate her
Ada follows the Neo-Umbrella trail to China, where a bioterror incident dwarfing the recent Tall Oaks attack is occurring. Picking up BSAA transmissions, Ada locks down her imposter's location.
On her way, she encounters Sherry from the Raccoon City incident, with Jake Muller in tow.
In addition to the young agent Birkin, both Leon Kennedy and Chris Redfield are in China as well.
Ada muses that the entire affair seems more like a Raccoon City reunion. Following Chris, Ada infiltrates the Neo-Umbrella-controlled aircraft carrier, intent on finding her imposter.
On the aircraft carrier, Ada finds documentation regarding the creation of her imposter.
It all stemmed from Simmons' deep-rooted frustrations in her not being the docile, obedient soldier he expected. This frustration bore a twisted need for revenge, which came in the form of creating a facsimile of Ada—a clone that would obey Simmons and only Simmons. The road to perfecting the clone was long, and littered with failures—countless test subjects used and discarded—until finally, success was had in injecting the C-Virus and a sample of Ada's DNA into Carla Radames, a scientist working under Simmons. However, this success was short-lived. The buried consciousness of Carla slowly awoke to her situation, and began to extract retribution against Simmons.
Ada finds her clone's body crumpled on the floor. The imposter had been cornered by the BSAA but ultimately gunned-down by The Family. However, Carla's body, which by all rights should have been dead, springs to life and attacks Ada. Powered by an enhanced strain of the C-Virus, Carla undergoes violent mutations, shrieking that she is the true Ada Wong.
Following a desperate struggle, Ada is eventually able to defeat her clone. However, still having some loose ends to tie up, Ada takes a helicopter and flees the aircraft carrier.
Flying into the city, now engulfed in a zombifying gas, Ada spots Leon and Helena locked in a heated battle with Simmons. Simmons, it seems, has injected himself with the same enhanced C-Virus as Carla. Ada rescues Leon and Helena, and cutting through the last of the Neo-Umbrella resistance, the trio fly to the Quad Tower. Here, the complete data set on Ada and her clone is housed. Ada decides that this information must be purged.
Simmons, though, is not finished and launches another attack. With the help of Leon and Helena, Ada manages to defeat Simmons for good, and then slips away.
Though the building is unstable, Ada makes her way into the Quad Tower laboratory and uncovers Carla's myriad notes and research, but most importantly, she finds Carla's ultimate work: a single cocoon housed in a glass chamber.
Without pity or remorse, Ada unleashes a barrage of fire into the equipment, destroying all of Carla's things along with the un-hatched cocoon.
As the Quad Tower begins to crumble around her, Ada coolly answers her phone and smiles.
It is orders for her next assignment.