The following events take place after Ratchet and Clank Future: A Crack In Time.
Ratchet and Clank are relaxing on Veldin. Ratchet is fixing his Servant Bot and Clank is watching re-runs of Secret Agent Clank on their TV. Talwyn appears on her jet-pack flying towards Ratchet. She gives Ratchet a rare material called Ioprui. Suddenly the TV Clank is watching show's a important galactic message from Sasha Phyronix. (Who has recently become Galactic President). Ratchet, Clank and Talwyn watch as Sasha announces that Captain Qwark and Skid McMarx have gone missing. She then announces that both of them were witnesses to the recent theft of funds from Gadgetron. Their testimony would have brought Major Criminal, Bolty Madoff to jail. Sasha asks the people of the galaxy to call Marcadia People Finder Corp. if they find Qwark or Skid. Ratchet immediately suggests finding Qwark and Skid in order to stop Bolty Madoff.
Here Ratchet and Clank complete their tutorial instructed by Cronk and Zephyr. Then Talwyn completes her tutorial. The trio meet up with Cronk and Zephyr who give the coordinates to Bolty Madoff's Mansion on Planet LotABolt's.
Here Ratchet and Clank search for information leading to the disappearance of Captain Qwark and Skid. Talwyn mysteriously has not arrived yet and is not answering her calls. Ratchet and Clank decide to go on without her. After exploring the mansion the find Bolty's secret chamber. In this chamber they find his computer which has been destroyed however they find Bolty's To-Do-List which his most recent schedule is to visit the Qwark Museum on planet Umbris. Before, they can leave B.A.D. (Bolty's A-1 Deathbot) attacks them. After beating B.A.D. Ratchet and Clank meet up with Talwyn who was delayed by an attack from planet Magmos. At this point you could decide to go to Umbris or Magmos.
Ratchet and Clank arrive in Umbris to find that the Qwark Museum is surrounded by the police. Officer Jones tells the trio that a villain by the name of Big Boom has taken the staff and visitors of the museum hostage in the Qwarktastic Virtual Reality Super Adventure! After searching though the museum the group enters the QVRSA and challenge Big Boom to a Virtual Challenge. Ratchet then takes Big Boom down in a Virtual Dual. Big Boom then reveals that he saw Captain Qwark on planet Venatonio.
When Ratchet, Clank and Talwyn arrive here they realize that the city has been overrun by Zyghr Raiders. After the trio liberate the city from the raiders the Magmos Chairman gives them the coordinates to planet Zyghr. He also promises he will give the group a pair of Levitation Boots and a Statue dedicated to them if they wipe out the Zyghr Raiders. Ratchet immediately agrees and rushes the group to get back to the ship.
Ratchet and Clank arrive in Venantonio while Talwyn finds the Ameboid Chairman to find out if he has seen Qwark. After searching the city and being attack by Ameboid Criminals the duo finds Captain Qwark who turns out be a Transforming Ameboid. The Transforming Ameboid then attacks them. Tawyn arrives to tell that the new sensation of the Transforming Ameboids is to watch TV and take the form of the person in the most important news. Captain Qwark being the current one. The group then gets a message from Cronk and Zephyr telling them that Skid has been spotted in Blackwater City.