In Assassin's Creed Brotherhood, Rome is the city rebuilt and controlled by Cesare Borgia.
The game is set primarily in early sixteenth-century Rome, where Cesare Borgia and his family exert political and military power. Ezio Auditore arrives after the destruction of Monteriggioni and works to weaken Borgia control across the city.
Rome functions as Brotherhood's main open world and includes districts that Ezio gradually liberates. Players restore shops, landmarks, and services, while recruiting citizens into the Assassin brotherhood. These activities represent the gradual recovery of the city.
Florence and Venice are strongly associated with Assassin's Creed II, while Naples appears in other historical settings. Rome is therefore the specific answer for Brotherhood's central city, rather than a general Italian location from the series.