Desmond wakes from his coma, but he is still inside the Animus. His companions believe that he’ll suffer irreparable damage if they can’t find a way to control the negative effects of the Animus. Ironically, that means that he is safer left inside the device.
He meets Subject 16. Desmond finds out that he won’t be able to wake unless he can finish Ezio’s and Altaïr’s memories. Subject 16 sacrifices his life so that Desmond can continue this journey.
Ezio’s memories continue years after the death of Cesare. The Assassin is hunting for the origins of a man named Masyaf. Ezio uncovers Altaïr’s library and finds out that the Templars are also trying to find something hidden there.
Ezio has to fight against several agents who are working for the Templars, and this results in his banishment from the city. He still finds what he needs to open Altaïr’s library, where he discovers everything that Altaïr did in his later life.
Ezio takes this information and tracks down Masyaf. This is where he finds Altaïr’s corpse and the Piece of Eden that the dead Assassin was carrying. Desmond and Ezio speak, and Ezio leaves his Assassin tools there.
Desmond soon meets another strange figure named Tinia (also known as Jupiter). Tinia explains that they are from a past society that tried to save the world but failed in their task. The Earth was greatly damaged during their time, and a similar catastrophe is coming. This can be stopped, but Desmond must find the vaults where their technology is hidden. That knowledge is inside a Grand Temple that houses an entire civilization’s worth of wisdom.
Desmond wakes, and his resistance allies are there waiting for him. He explains all that he has learned about the danger to Earth and how it can be stopped.