The storyline revolves around the safe return of Boo, a small child that wonders in through a door that was left on after the scream floor was to be cleared.  The story begins in level one by introducing you to the controls in the game.  The first task Sulley must complete is to return a time card to a monster (a new recruit) who lost his.  After completing this level, the cut scene shows the door being left open for Boo to walk through and enter the monsters' world.  Each additional level is doing a task, whether from jumping to cliff to cliff to get an object of Boo's costume or turning on five fuses to restore power to the factory so Sulley can open a door to get to Boo, to get Sulley closer to returning her back to her room.  Completion of the ten levels brings Boo safely home.  Each level is a breakdown below.

Level 1
Find the new recruit's key card and return it back to him. (Mainly to introduce you to the controls and what/how points are gathered.)

Level 2
Sulley has discovered Boo and must get her back to his apartment as soon as possible.  He must navigate over buildings to get home, turning off power to slide down power lines.

Level 3
Boo needs a costume so Mike sends Sulley on a search through the apartments in his building.  The apartment building has 3 floors (and a basement).  Sulley must go to each level to get a piece of Boo's costume.  The catch is that to get some pieces of her costume, Sulley must bring Boo with him so she can scare the monster with the costume piece since some monsters are afraid of children.  Sulley must complete the gathering of the 4 costume pieces before the CDA catches him and return each one to Mike.

Level 4
Sulley and Mike return Boo back to the Scream Factory to return her home, only she gets lost.  Sulley must navigate through the mailroom with conveyor belts and open hidden doors by scaring the fuses.  He navigate through the mailroom onto a cart that he must jump from side to side to avoid getting knocked off the cart from an arm hanger.  Once Sulley reaches the end, he retrieves Boo.

Level 5
Boo is then stolen from Sulley and Mike by Randall Boggs, the bad monster who is always trying to better his own situation.  Boo is taken to a creation by Randall and Waternoose (Sulley and Mike's boss) to try and steal the scream out of her.  Sulley must navigate across pipes, conveyor belts, jump pads, and floating ledges to get to her.  Each time he turns on a fuse by scaring it, another portion of the path becomes unlocked so Sulley can find his way to get her.

Level 6
Waternoose banishes Mike and Sulley from Monstropolis by opening a door and pushing them out.  The player must navigate Sulley down to the city below by dodging snowballs and running across bridges before they break.  When he reaches the village, he goes through a bedroom door to get back to Monstropolis to save Boo from Randall's machine to steal children's screams.

Level 7
Sulley must chase Randall, who has Boo in his possession, through the storage room with the doors.  The doors are all on tracks and Sulley must jump from door to door to get to her and Randall.  Once Sulley catches up with Randall, he must push Randall off the platform to save Boo from him.

Level 8
Sulley must defeat Waternoose by turning on all the fuses to lower him into the incinerator.  Sulley must jump on the jump blocks to jump higher and scare the fuses to open up doors to more fuses.  Once Sulley scares all ten fuses, he lowers Waternoose into the incinerator and wins the game.  By Sulley destroying Waternoose, Monstropolis can now start using a new form of energy with children's laughter because they are more powerful than scaring the children.