In Assassin's Creed Brotherhood, Ezio works to liberate Rome from Borgia control.
Rome is the central setting of Brotherhood, which continues Ezio Auditore's story after Assassin's Creed II. The city's districts are controlled by the Borgia family and their allies, and Ezio gradually weakens that rule by destroying military infrastructure, recruiting new Assassins, and restoring local businesses and landmarks.
The historical backdrop includes Pope Alexander VI, whose birth name was Rodrigo Borgia, and his son Cesare Borgia. The game dramatizes their power in Rome, while presenting Ezio's campaign as part of the wider Assassin–Templar conflict. The story also includes the Vatican and the Colosseum, although the game uses some locations and events for fictional adventure.
Brotherhood is sometimes confused with Assassin's Creed II because both games feature Ezio and Renaissance Italy. Their main settings differ: Assassin's Creed II moves among several Italian cities, while Brotherhood is primarily built around one large open-world Rome. The city also provides the foundation for the game's expanded Assassin recruitment and management systems.