The events of the game takes place sometime in fall 2005 after the summer. Damian claims that the school year of today will be the best, since he's the acting head of the Students Activities Committee. He decides to make this school year drama-free for North Shore. Janis asks if the drama counts from the Drama Club, since Damian is also the president of the Drama Club. Damian disagrees with Janis about the topic, saying that the drama from the Drama Club doesn't count. Janis and Damian find Cady and they ask her if she's all set for another fun-filled school year at North Shore. In which Cady agrees. Janis then claims that things on the school have gotten really weird since the last year's Spring Fling. She claims that the students are way too friendly for her taste. Cady then says that she's glad that everyone is finally getting along. She claims that during the summer, she saw Trang Pak help Dawn Schweitzer pick a new back to school wardrobe at the mall. But Cady claims that Janis was right about the events from last year. That North Shore became different, that everyone achieved some sort of peaceful harmony.
Cady gets to see the original Plastics that broke up and asks them about their summer. Gretchen claims that she went to the Mediterranean with her parents in Turkey and got a ring she found or bought during the trip, claiming that her ring is So Fetch. Regina was annoyed by Gretchen saying her long-lost slang again. And Karen wonders why Gretchen went to Turkey if it wasn't Thanksgiving yet. Cady, whoever, was definitely glad to be back. Not only that, a new group of Plastics show up and the leader claims that how's a school going to function without a queen bee. The redhead Plastic claims that how she and her friends are supposed to be popular when even the weirdos and losers fit in. The black Plastic claim that North Shore took a dive when Cady broke the tiara and basically ruined everything. The queen bee thought it would be nice for the Plastics to put the tiara back together, to become queen bee at North Shore.
After school that night, Gretchen called Cady and told her that Trang Pak saw the New Plastics heading towards the gym. Cady responds saying that she dreaded going back there after the Burn Book assembly from last year, and Gretchen calls Regina. Once Regina is on the phone, Cady warns Regina about more Plastic drama taking place at the Gym, and says that their game needs to step up. All of a sudden, Karen responds on the phone saying that she's really good at checkers, and Regina apologized saying that she was on the phone with Karen. Cady asks the broken-up Plastics if the have any ideas, but Karen wants to go out with them and get some tacos. Finally, Regina knows exactly what to do and tells Cady, Karen and Gretchen to meet her in the Gym tomorrow.
The player starts the game by selecting a level on Cady's map to North Shore High School, along with its difficulty, Cliques, and the character available this week. After the player picked what's necessary, the player's character will appear on the level with a carpet connected to a display, where the tiara is. With a decent amount of popularity, (100 or 75, depending on the level) he or she must spend it on Cliques in order to defend the tiara from the waves of Plastics the player may encounter. The Plastics range from the weak ones to the strong ones, all of them are trying to reach the tiara by following the path towards it. The tiara has 10 pieces in total, and if 10 Plastics manage to reach the tiara, they reassemble the pieces and become the queen bee of North Shore High School.
Depending on the difficulty, Easy mode has 20 waves, Normal mode has 25 waves, and Hard mode and challenges has 30 waves.