Following on from Desmond's previous foray into his ancestral assassin-past, Aquilus desperately strives to avenge his father's murder. His thirst for revenge leads him to Rome, and sets him on a quest for the mystical Ankh as the savage Barbarian tribes, led by the deadly Assassin Accipiter, prepare to descend upon Lugdunum. Desmond, meanwhile, must also fight stay alive in the present day.