Ratchet and Clank are celebrated as galactic heroes during a parade hosted by Captain Quark, Skid McMarx, and Rusty Pete on Corson V. During it, Clank reveals that he has repaired the Dimensionator, a device capable of opening rifts to other dimensions so that Ratchet can search for the Lombax race and his missing family. However, Doctor Nefarious attacks the parade and attempts to steal the Dimensionator. During the struggle, Ratchet unthinkingly shoots the Dimensionator, which causes dimensional rifts to begin opening randomly. Ratchet, Clank, and Dr. Nefarious are transported to an alternate universe, where the Dimensionator explodes, damaging the fabric of space and time and separating the three. Clank awakens to find himself alone and now missing his right arm from the blast. He is discovered and picked up by a female Lombax named Rivet. Meanwhile, Dr. Nefarious ends up in a throne room, where he is mistaken for Emperor Nefarious, an alternate version of himself who, unlike him, has never been defeated and rules over the galaxy. Ratchet, elsewhere, finds himself alone and starts his search for Clank.
It retains elements of previous Ratchet & Clank games, such as strafing, gunplay, collection of bolts, automatic weapon and health upgrades, manual Raritanium weapon upgrading and gadgets. The main playable character is Ratchet. He is accompanied by his robotic friend and sidekick Clank, who is hung on his back. Additionally, the game has a playable female Lombax named Rivet, as well as a robot similar to Clank, Kit. The player navigates Ratchet and Rivet through diverse environments across a multitude of levels, defeating enemies with an array of varied weapons and gadgets, and traversing obstacles to complete key mission objectives.