Manuela is the only daughter of Drug Lord Javier Hidalgo and an unnamed woman. Manuela is first discovered in a South American Church by Leon S. Kennedy and Jack Krauser who are on a mission to capture Javier. The duo were originally to meet a guide in the village but the village came under siege due to the villagers harboring Manuela who had recently run away from Javier's Mansion for (at first) unknown reasons. She is singing in the church when Jack and Leon arrive and the duo are soon attacked by new B.O.W. After driving off the creature Leon and Krauser convince Manuela to take them to Javier's Mansion. During the trek there they encounter Javier to reveals to the operatives that Manuela is his daughter and that she has been injected with the T-Veronica Virus.
Manuela explains that she has contracted a disease that is only found in the region of her country and that this disease also killed her mother. Javier injected her with the T-Veronica Virus in order to eliminate the disease that would have killed her. In order for Manuela to survive the process her organs must be removed and replaced with non-contaminated organs. Javier has abducted all of the young women in the region and is using them as donors for his daughter.
Manuela managed to convince her doctors to tell her how she had survived the original disease and upon learning fled in horror. Javier infected his men with the T-Virus, injected himself with the T-Veronica Virus as well and acquired B.O.W.'s from a former Umbrella Researcher.
Rather than return to her father Manuela seeks to either die or escape with Leon. Leon is (up until now) been under secret orders from the President of the United States to eradicate the T-Veronica Virus and Krauser (upon learning this) agrees to help him with the mission.
Manuela manages to subdue the returning sea creature and Leon and Krauser engage it again. During the fight, Krauser is shot in the left arm with a bio-spear like weapon from the creature (mirroring the unrelated Plagas mutation that he has in Resident Evil 4) but the duo manage to kill the beast.
When Javier engages the duo Manuela helps them defeat her father.
[Note: Depending on how long the player takes to defeat Javier depends on Manuela's fate.
Good Ending: If the Player kills Javier in less then 10 Minutes, she lives and is brought back to the United States.
Bad Ending: If the Player does not kill Javier in under 10 Minutes Manuela sucfumbs to the T-Veronica Virus and dies.