When a comedic shopping expedition for Thor's birthday gift goes awry, Hulk and Iron Man accidentally stumble onto Thanos's vessel just as the tyrant secures the Infinity Gauntlet. The two heroes urgently return to headquarters and alert the Super Hero Squad to the catastrophic threat: should Thanos gather all the scattered Infinity Stones, his power will become absolute and unstoppable. The squad's finest heroes—Spider-Man, Wolverine, Thor, She-Hulk, Falcon, and the Invisible Woman—band together in pairs and race across the cosmos, venturing through mystical realms like Asgard and hazardous dimensions such as the Negative Zone, to track down and secure the stones before Thanos's criminal allies can. Blocking their path are relentless supervillains, each driven by their own hunger to harness the gauntlet's reality-warping power for themselves.