The setting of Resident Evil 5 has a similar feel to the film Black Hawk Down. Takeuchi added that the development team is composed of staff members who worked on the original Resident Evil. The game is a direct sequel to the Resident Evil series, and continues chronologically after Resident Evil 4. The player characters and protagonists are Chris Redfield and Sheva Alomar, and the game takes place in 2009, eleven years after the events of the original Resident Evil.
During the game's events, he is a member of a group known as Bioterrorism Security Assessment Alliance (BSAA), and sent to investigate a terrorist bio-organic weapon (BOW) threat in an African desert area in Kijuju, that serves as the game's setting. The antagonists of the game include Albert Wesker, a returning antagonist to the series, and Excella Gionne, a relative of the founder of the Tricell Pharmaceutical Company who operates the company's African branch. Ozwell E. Spencer, the founder of Umbrella Corp. and a key figure in the background story of the series since the original Resident Evil, is also included in a flashback