In Assassin's Creed Brotherhood, Rome is controlled by Cesare Borgia and targeted by Ezio's rebuilding campaign.
The game takes place primarily in Rome, where Cesare and his allies exert political, military, and economic power. Ezio works with the Roman Brotherhood to weaken Borgia influence, liberate districts, recruit new Assassins, and restore shops and services across the city.
Rome's districts begin under hostile control and gradually become more accessible as Ezio destroys Borgia towers. Rebuilding the city is not merely decorative: restored businesses provide income and unlock useful services, while liberated areas expand the Brotherhood's practical reach.
Brotherhood follows Ezio after Assassin's Creed II and continues the Renaissance storyline. Florence and Venice remain important to Ezio's earlier history, but Rome is the central setting here. Constantinople belongs chiefly to Assassin's Creed Revelations, making it a separate location in the trilogy.