Nero is the main antagonist of Ryse: Son of Rome and based loosely on the Roman Emperor of the same name, he is not actively faced for the majority of the game but his role as antagonist is establishd via a story (which serves as the game itself) told to him by Marius, a soldier who came to guard him after a barbarian attack on the Roman capital.

Nero's two sons also act as supporting antagonists, especially the psychopathic Commodus.