In Assassin's Creed Brotherhood, Rome is the city Ezio governs as the leader of the Assassins.
Brotherhood is centered on Ezio's campaign against the Borgia family in Renaissance Rome. After arriving in the city, he rebuilds the local Assassin network, recruits and trains new members, and weakens Borgia control over districts and institutions. Rome is consequently both the principal setting and the strategic focus of the game.
The game follows Assassin's Creed II, where Florence and Venice are especially important. It also includes a modern-day storyline at the Villa Auditore in Monteriggioni, but neither location replaces Rome as the main city of Ezio's Brotherhood campaign.
Rome's landmarks, including the Colosseum and the Vatican area, are integrated into missions and exploration. The historical setting is fictionalized, yet characters such as Cesare Borgia and Rodrigo Borgia are based on real Renaissance figures.