After the unconventional side-scrolling and 2D platforming that was Super Paper Mario, the Paper Mario series returns to its roots in Paper Mario: Sticker Star...at least when it comes to overworld movement. In the first handheld title in the subseries, the citizens of Decalburg are celebrating the Mushroom Kingdom's national holiday the Sticker Fest, where everyone gathers together at night to watch the Sticker Comet descend to the planet, which happens annually. Legend states that the Sticker Comet grants everyone's wishes, and Princess Peach is on stage to present it to Mario and some Toads. But Bowser Crashes the party and attempts to steal the comet. When some Toads try to stop him, the comet is accidentally shattered into six pieces, one landing on Bowser's head, causing him to gain immense power. Knocked unconscious, Mario is joined by Kersti, a sticker fairy from a place called the Sticker Star. She gives him some special abilities, and they set off to recover the pieces of the Sticker Comet.

Unlike the other games in the series, Mario is the only real playable character, his only true companion being Kersti. The free combat seen in Super Paper Mario is abandoned in favor of encounters like those seen in Paper Mario and Paper Mario: The Thousand Year Door. However, battles are different: attacks and defensive moves are now done via stickers (such as jump and hammer stickers) that vary in power. There are also "Thing stickers" that summon 3D objects that can be used either in battle or the field. There is also the "Paperization" ability. If something doesn't look right, such as an upside-down background, Mario can turn the screen into an image and peel the object off like a sticker and turn it to the correct angle. Sometimes he will also find objects missing, with a dark purple void shaped like the object. He must find the "Paperized" object and place it there to progress. Another new addition is the Sticker Museum, where the player must place every kind of sticker, both battle and Thing, to complete.