In Assassin's Creed Brotherhood, Ezio works to liberate Rome from the Borgias.
Brotherhood continues Ezio's story after Assassin's Creed II and concentrates on Rome, where the Borgia family controls political and military power. Cesare Borgia serves as the principal human antagonist, while his father, Rodrigo Borgia, is the series' leading Templar figure.
Ezio rebuilds the Assassin Brotherhood in Rome by recruiting allies and weakening Borgia control over districts. Players can renovate shops, restore landmarks, and remove enemy influence, making the city's gradual liberation part of the game's progression system.
Rome is not merely a backdrop: it is the game's main open-world location. Florence and Venice return as smaller mission locations, but the central campaign, Brotherhood system, and major confrontation with Cesare are tied to Rome.