Ratchet and Clank: Siren's Call is the eleventh game in the series, taking place about a year after Into the Nexus. It takes place in the years 5365 to 5366.
The game starts with the duo asleep in Ratchet's Garage on Veldin when there is a knock on the door. Upon opening the door they meet a bird-like alien who calls himself Nelaiar and claims to be an old friend of Kaden's. He tells them of how Kaden entrusted a small, spherical piece of complicated and delicate machinery to him, telling him to give it to his son when he's made a name for himself. He states how proud Kaden would be of Ratchet could he see him now, but also says that Kaden left in a hurry without giving a clue about what the sphere was for. It is implied that Kaden was killed by Tachyon not soon after.
When Ratchet touches the sphere a holographic recording of Kaden flickers into action. He tells Ratchet that the sphere is a Memory Core, containing the coordinates to a Vault of Knowledge on Fastoon that was built near the end of the War against Tachyon, which contains all the research of the Lombax scientists prior to the Exodus and something special for Ratchet that he hid in preparation. He tells him that the Keys to the Vault is spread out across four different Lombax Colonies, but he doesn't know which ones. He tells him that he is going to face Tachyon, and says ominously that if he loses Ratchet is the only hope against the coming darkness. Then the time apparently runs out as Kaden is cut off mid-sentence. However, Ratchet is unable to open the Memory Core and dares not be too forceful in case it breaks. So the quest begins.
First the duo travel to Kreeli Comet to seek information from IRIS on how to open the Memory Core as well as a list of all Lombax Colonies. Upon arrival they find that a Vosk terrorist organisation calling themselves 'the Listeners' has set up camp around IRIS and taken it for themselves. Their attempt to sneak by is derailed when they are spotted and attacked by one of the Listener's Scout Bots. After a fierce fight through the Listener ranks and a quick grinding segment through a collapsing ice cave they arrive at the entrance of IRIS where they are stopped by the Listener General, a Vosk named Kirim Hark who confronts them, he tells them IRIS is necessary for a mysterious cause and that if they really wanted to use it they should have asked nicely. When questioned if the Listener's would let the trio use IRIS he laughs and attacks them. After a hard fight General Hark withdraws, stating his survival is necessary, but theirs is not and then locks them in the computer room. A sudden alarm goes off and Ratchet has to find an escape route as Clank finds the information they need. Finally they manage to call for Aphelion to blast open the doors and carry them away as the most intelligent computer in the galaxy blows up behind them.
With the Memory Core open they fly to the Vault on Fastoon. They land in a sinkhole and after navigating ruined bridges and deadly creatures in the nearby caves they arrive at the sealed door of the Vault. Some nearby buildings contain the logs of the foreman of the miners who dug out the caves. Mostly uninteresting information when suddenly the foreman mentions a mysterious ship with unknown cargo setting its course for a Lombax Colony called Barastrix, when wondering about the ship he was told it was top secret business and stayed out of it. The ship's cargo must have been one of the keys.
The duo goes to Barastrix, where they find the Listeners in the process of tearing the ruins apart. Once more Ratchet fights through the Listener ranks until they reach a tower in the centre of the downtown ruins.