"Resident Evil: Vendetta" is a CGI anime film set in the "Resident Evil" universe, blending action, horror, and science fiction. The narrative centers on Chris Redfield, a veteran BSAA agent, who teams up with federal agent Leon S. Kennedy and professor Rebecca Chambers to stop a bioterrorist plot. The story begins with Chris investigating a trafficking ring in Mexico, where he encounters Glenn Arias, a former arms dealer turned bioterrorist. Arias seeks revenge for the loss of his family by unleashing a new virus, the A-Virus, which transforms infected individuals into aggressive, zombie-like creatures.

Leon enters the story after a mission in New York City goes awry, resulting in the death of his team due to Arias's bioweapons. Rebecca, a virologist and former S.T.A.R.S. member, becomes involved when she discovers a connection between Arias and a dangerous virus strain. The trio converges to confront Arias, who plans to release the A-Virus globally during a high-profile event in New York. The plot unfolds through intense action sequences, including a climactic battle in Arias's mansion, where the protagonists face off against mutated bioweapons and Arias himself, who has enhanced his body using the virus.

The film explores themes of revenge, bioterrorism, and the ethical implications of biological experimentation. Chris, Leon, and Rebecca each bring their expertise and combat skills to the mission, highlighting their roles as seasoned survivors in the fight against bioterrorism. The narrative maintains a fast pace, with a focus on high-stakes confrontations and the personal stakes for the characters, particularly Chris's determination to stop Arias and prevent further loss of innocent lives. The film concludes with the protagonists thwarting Arias's plan, though the lingering threat of bioterrorism remains a constant in the "Resident Evil" universe.