Confrontation in the Vatican

After reclaiming the Apple of Eden from Girolamo Savonarola in Florence, and collecting all the pages of the Codex, Ezio Auditore and the rest of the Assassins prepare themselves to strike Rodrigo Borgia and learn where the fabled Vault lies.

Journey along the Passeto di Borgo
"I thought...I thought I was beyond this. But I'm not. I've waited too long... lost too much... Requiescat in pace, you bastard!"

- Ezio's first assassination attempt on Rodrigo Borgia.

With some members of the Order meeting in Mario's study at Monteriggioni, Ezio inspected what was written beneath the Codex Pages that were placed on the wall. He assembled them as members of the order looked on, and successfully finished, revealing the map of the world, which showed the locations of other Pieces of Eden (41 in total). Ezio marveled that the landmasses depicted on the map didn't exist. Niccolò Machiavelli answered that they did, but most likely had yet to be discovered, "or rediscovered" as he added.

To Ezio's shock, he then saw that the much-talked-about Vault was located roughly right where the city of Rome stood. It was then that he theorized that Rodrigo Borgia became Pope so as to get his hands on the Papal Staff, as well as gain access to the Vault. When Teodora questioned Ezio's meaning, Mario Auditore explained the prophecy from the Codex, stating that two Pieces of Eden were needed to open the Vault, one of the Apples, and the Staff. The other Assassins began to speculate about what the Vault would contain, and expressed their fears of what Borgia would do once he had attained it.

Ezio decided that he would confront Borgia and try to open the Vault himself. The other Assassins agreed, offering to "cause trouble in the city" to keep the Borgia guards from stopping Ezio. With his mission planned, and his final vengeance in sight, Ezio departed for Rome.

Ezio arrived in Rome outside Castel Sant'Angelo, and began to scale the building until he had climbed onto the Passeto di Borgo. Using horses, he was quickly able to traverse the wall and kill all of the troops on it, finally reaching an entry point into the Capella Sistina. Traversing along beams and ropes high above the ground, Ezio made his way within striking range of the Pope, and then leapt at him from above, hitting Borgia with some force, and seemingly knocking him unconscious.

Holding Borgia at his mercy, Ezio allowed his anger and hatred for Borgia to overwhelm him, remembering all too well Borgia's part in his family's destruction. But, as he made to deal the death blow, Borgia reawakened and with a snarl, smashed Ezio aside with the Staff. Before anyone in the Chapel could react, Borgia used the Staff's powers to drain the life energy from the assembled priests and guards to heal and energize himself; only Ezio, protected by the Apple's power, was immune. Rodrigo demanded that Ezio hand the Apple over to him, but the Assassin only bluntly told the Pope to take it from him. He then used the Apple's power to produce four spectral doppelgangers of himself (such as how Al Mualim did against Altaïr Ibn-La'Ahad). Ezio and Borgia engaged in a brief duel, and after fighting his way through Ezio's duplicates, Borgia collapsed from exhaustion.

Ezio told Borgia to put down the Staff and accept his offer of a quick death, but Borgia, asking if Ezio would give up so easily if their positions were reversed, again made use of the Staff's power, blasting Ezio off his feet and turning himself invisible. As Ezio struggled to recover, Borgia seized the Apple from him, and combined it with the Staff, magnifying its powers greatly. With that, Rodrigo used the Staff to lift Ezio up and suspend him in midair. As the Assassin dangled helplessly, Rodrigo stabbed him in the side with a knife, then ended the Staff's hold, dropping the badly injured Ezio to the floor. Just before he passed out from blood loss, Ezio saw Borgia descend down a hidden staircase in the Capella's floor.

The Vault
"It's over, Rodrigo. No more tricks. No more ancient artifacts. No more weapons. Let us see what you are made of, old man."

- Ezio challenges Rodrigo Borgia to a final fight.

Some time later, Ezio regained consciousness. His wounds were not fatal, thus he got back to his feet and investigated the altar that he had seen Rodrigo disappear into. Finding the hidden doorway, Ezio followed the Pope down the staircase into a strange underground corridor, until he came to a large, open chamber below him; the atrium of the Vault. There, he could see Rodrigo, desperately trying to open the door. Ezio dropped down and, casting aside his sword, short blade and pistol, challenged Borgia to one last fight, free of trickery, ancient artifacts or weapons. Borgia reluctantly accepted, and the pair brawled with nothing but their fists.

As they fought, Ezio demanded to know what lay in the Vault that the Templars wanted so badly. Rodrigo showed surprise that the Assassins were unaware of the truth, and claimed that God was what lay within. Ezio was somewhat skeptical, and asked what Rodrigo intended to do with this knowledge, to which Borgia replied that he intended to release God and seize his power, a feat made possible through the Staff and Apple. Ezio remarked that he was doubtful a couple of ancient relics could harm a god, but Rodrigo sneered that he knew nothing, that his images and views on God were taken from a book written by men. When Ezio challenged Borgia for dismissing Christianity's central text, Rodrigo laughed, saying he had only become Pope to gain access to the Vault and the power such a position granted. He claimed not to believe a single word of the Bible, deriding it and every other religious text as superstitious lies.

After a lengthy fight, Ezio gained the upper hand. Seizing Borgia by the throat, he throttled his old enemy into submission, and finally held him at blade point. Astounded, Borgia yelled that Ezio could not open the Vault, as it was his destiny as the Prophet to open it. But Ezio set Borgia straight; stating that he was not the Prophet, nor had he ever been. Broken and humiliated by this revelation, Borgia told Ezio to kill him and be done with it, but Ezio refused to kill for the sake of vengeance, and relinquished his long-felt hate and desire for Rodrigo's death, stating simply that "Killing you won't bring my family back." Leaving his defeated nemesis on the floor, Ezio remarked to Borgia as to how he'd had been beaten – because "Nothing is true, everything is permitted" – and paid him no more heed. Turning to the Vault, Ezio used the combined power of the Staff and Apple to open a chamber directly in front of him, and then entered.

The Warning
"Enough! I do not wish to speak with you, but through you. You are the Prophet. You've played your part."

- Minerva asks Ezio not to interrupt her warning to Desmond.

Entering the Vault, Ezio was confronted by a speaking image of a female figure. After confirming that he was the Prophet by showing the figure the Apple, the woman remarked that they must speak, though she seemed not be speaking to him. Ezio asked who she was; the woman replied that she had died with the name Minerva, but had been known by many others, as had the others buried with her, such as Juno and Jupiter. Astounded, Ezio theorized that they were gods. Minerva laughed at this, saying that she and her kind were not gods, but that they simply came before. She remarked that humanity had not understood them when they existed, but while they couldn't comprehend her, they would comprehend her warning.

Ezio remarked that her words made no sense to him, but Minerva replied they weren't meant for him, confusing Ezio further, since no one else was there. Minerva snapped that she wasn't communicating with Ezio, but through him; thus his part in all this was finished. She explained that Ezio was an anchor for the one she wished to communicate with, and politely asked him to be silent to assist this. Ezio listened as she delivered a confusing warning of an impending celestial disaster to an individual called 'Desmond', before fading away. As she departed, Ezio begged her to wait, since he still had so much to ask, but she vanished without stopping, leaving Ezio's questions unanswered.

The escape from Rome
Once Ezio made the discovery of the Vault he emerged from the main chamber, only to find Rodrigo gone and his uncle Mario standing there. Ezio told Mario what he had seen and the questions that needed answering, but they were attacked by gaurds send by Rodrigo, Ezio and Mario easily over powered them and decided it would be smart to make an escape. They made their though the Vatican killing all guards send by the Spaniard, until they reached Timber river, where Mario encouraged Ezio to drop the Apple in, so it would be lost forever, but Ezio could not get rid of a artifact of such power, Mario then decided he would take care of the Apple until Ezio made his decision. Afterwards they both returned back to Monteriggioni.

Aftermath
Having succeeded in their mission to reach the Vault and prevent the Templars obtaining its contents, the Assassins withdrew from Rome, and Ezio retired to Monteriggioni, hoping to recover from his trials. However, unknown to all, the vengeful Rodrigo Borgia was plotting a way to bring the Auditore, Ezio in particular, to its knees once and for all.

In 2012, after viewing Ezio's genetic memory of these events, his descendant Desmond Miles was pulled out of the Animus 2.0 because the hideout was under attack by Abstergo. Warren Vidic had sought to recapture Desmond and Lucy Stillman, but his men were defeated. Unfortunately, despite this, the Assassins had to escape from any potential reinforcements, and were thus unable to pursue Vidic.