In Assassin's Creed Brotherhood, Rome is the main open-world setting ruled by the Borgia family.
The game continues Ezio Auditore's story after Assassin's Creed II and places him in Rome, where Cesare Borgia and his allies exert military and political control. Ezio works to weaken Borgia influence by destroying strategic assets, recruiting new Assassins, and rebuilding the Brotherhood in the city.
Rome is not simply a backdrop: its districts, monuments, guards, and economic systems are tied to the campaign's progression. The title also introduces a larger recruitment and command system, allowing Ezio to train Assassins and call them into missions. Florence and Venice belong prominently to Ezio's earlier adventure, while Constantinople is the principal setting of Assassin's Creed Revelations. This distinction helps separate the Italian chapters of the series from the later Ottoman-era story.