Mimi Mone vs Lauren Malloy takes place after Scream :Family Ties. Mimi is still alive and also Hayley's twin sister, Lauren is still alive. Mimi have revenge on Lauren. Lauren and Mimi start kill people and kill each other. Who can stop them? Also Brianna Albertson survived Sidney's stab, she believes the only way she can truly be redeemed is to stop the killers and since she is a killer she knows how they think. Jill is in the hospital and she continues to tell Sidney, Sam, Debbie, Thomas, Frank, Kirby and Robert her life story.
- Gary Sinise as Detective Frank Nightingale
- Alicia Silverstone as Detective Emma Lloyd
- Neve Campbell as Sidney Prescott
- Matthew Lillard as Det. Sam Macher
- Brooke Theiss as Debbie Macher
- Jeremy London as Lt. Thomas Miller
- Emma Roberts as Jill Roberts
- Georgie Henley as Hayley McDonald/Lauren Malloy
- Hayden Pantierre as Kirby Reed
- Emma Bell as Cami Watson/Mimi Mone
- Josh Brolin as Robert Morgan
- Chance Crawford as Lloyd McDonald
- J.C Brandy as Brooke McDonald
- William Sadler as Roy McDonald/Hayley, Lloyd, Brooke and Lauren's uncle
- Michael Madsen as Det Dennis Mitchell
- Molly Burnette as Caroline Mitchell
- Ellen Wroe as Brianna Albertson
- Juliann Hough as Carly Nelsen
- Matthew Gray Gubler as Jerry Clooney
- Shantel VanSanten as Emily Nightingale
- Kenny Wormald as Doug Henson
- Mike Beatty as Jonas King
- Paget Brewster as Cynthia Hudson
- Kendall Schmidt as Perry Johnson
- Ashlee Simpson as Valerie Michaels
- Matthew Knight as Ethan Carsia-He shows up in a video that Brianna is watching, she wishes he was still around. He also shows up in one of her dreams and he says he's happy that she wants to redeem herself.
- Emma Bell as Fifi Mone-She makes an apperance for a second but Mimi is able to take control again and she slips back into her brain. She is also seen with David and her sister Sally watching Jill who is seeing Trevor cheating on her with Jenny Randall.
- Zachary Abel as Kirk Loner-He shows up in a flashback scene
- Matt O'Leary as Richard Mosses-He also shows up in a flashback scene
- Carlos Marks as Henry Coop-He is seen in a flashback scene
- Kristen Dunst as Ruby Higgies-She is shown in a scene before she was killed.
- Rutina Wesley as Marcie Perkins-She is shown on a news clip
- Abigail Breslin as Alice Nightingale-She is shown on a videotape that Emily is watching.
- Ashley Greene as Sophie Taylor-She is shown in a flashback scene.
- David Henrie as Jimmy Mone-Mimi imagines him asking her to please let Fifi come out the killing needs to stop.
- Ashley Roberts as Sally Mone-She shows up in Mimi's dream telling her to please stop the killling also. She is also seen with David and her (baby) sister Fifi watching Jill who is seeing Trevor cheating on her with Jenny Randall
- Noah Cyrus as Young Brianna Albertson-Brianna dreams of when she was younger.
- Rory Culkin as Charlie Walker-He is shown in the scene where Jill tells Sidney,Frank and Robert when she went to Charlie to ask him if he would be interested in being famous, He is also shown when she tells them when her and Charlie decided to kill their friends.
- Marielle Jaffe as Olivia Morris-She is shown when Jill thinks back to the time she told Kirby and Olivia that Trevor cheated on her with Jenny.
- Nico Tortorella as Trevor Sheldon-He is shown when in a scene where Jill confronts him after seeing him kiss Jenny.
- Brittany Robertson as Marnie Cooper-She is shown when Jill asks to talk to Jenny alone.
- Aimee Teegarden as Jenny Randall-She is shown when her and Jill have a big arguement about Trevor, Jill also threatens to kill Jenny if she keeps badmouthing her and her mom.
- Zac Efron as David Samuels-He is seen with Fifi and Sally watching Jill who is seeing Trevor cheating on her with Jenny.
- Ashley Tisdale as Casey King-She is on a videotape
- Mila Kunis as Kristina Newman-She is shown on a news clip
- Ali Larter as Carrie Watson-She is shown in a flashback scene
- Brandon Buddy as Cole Benson-He is shown in a flash back scene
- Alison Lange as Maureen Peterson-She is shown in a flashback scene before she is killed.
- Debby Ryan as Tammy Wesner-She is shown in a flashback scene when she was killed by Mark Onie
- Bridgit Medler as Cammy Wesner-She is shown in a flashback scene when she is killed by Kristen Lovely
- Bobby Campo as Micheal Rover-He is shown in a flashback scene before he is killed by Trixie as Ghostface.
- A.J. Cook as Mary Polne-She is shown in a news paper clipping
- Matt Bennett as Sam Fixes-He is shown on a videotape
- Gage Golightly as Ursula Fixes-She is shown in a flashback scene
- Vincent Martella as Gary Time-He is shown in a picture in the news paper
- Lisa Wilcox as Det. Natalie Carmen-She is shown when she shot Mimi in the head saving Dennis and Caroline.
- Detective Frank Nightingale
- Emma Lloyd
- Emily Nightingale
- Sidney Prescott
- Det. Sam Macher
- Debbie Macher
- Lt. Thomas Miller
- Hayley McDonald/Lauren Malloy "Lauren was alive in this movie, she was sent to a psychiatric hospital"
- Kirby Reed
- Cami Watson
- Robert Morgan
- Roy McDonald
- Det Dennis Mitchell
- Caroline Mitchell
- Brianna Albertson
- Lloyd McDonald
- Brooke McDonald
Emma attacked by Mimi after found Doug's body
- (Emma open the door)
- Emma: Hello, Hello.
- Emma: Frank, Hayley, Sidney.
- Emma: Dennis.
- Emma: This is fucking joke, I am calling the police.
- (Blood on the floor)
- Emma: Hello.
- (Doug's body with Mimi)
- Emma: Mimi.
- (Mimi saw Emma)
- (Emma hold the gun)
- (Mimi scream with knife and stab Emma in the hip)
- (Emma groan)
- Emma: Shit.
- (Emma groan)
- (Mimi punch Emma)
- (Emma fall)
- (Mimi put the glass on Emma)
- (Emma groan and blood on mouth)
- (Mimi attack Emma)
- Mimi: You got a killer who about to kill you.
- Lauren: Two killer.
- (Lauren hit the box at Mimi)
- (Mimi groan)
- (Lauren stab Emma in the leg with glass and Emma scream)
- (Emma cough and groan)
- (Lauren attack Mimi)
- (Mimi hold the gun to Lauren and shot her 23 time)
- (Lauren try to open the window in bathroom)
- (Mimi shot Lauren 3 time and Lauren groan)
- Lauren: Buttetproof vest.
- (Mimi walk to Emma)
- (Mimi punch Emma 7 time)
- (Emma's blood face)
- (Mimi saw Hayley and Frank in the car)
- Mimi: Shit, they are coming.
- Mimi: I need leave everything.
- (Mimi run and hide)
- (Emma fall and crash everything)
- (Frank open the door)
- (Frank and Hayley walk)
- Hayley: Listen, we got two killer.
- Hayley: You are worried about your girlfriend.
- (Mimi walk slow)
- Hayley: I know Emma did not turn up in crime scene.
- (Mimi walk careful)
- Frank: I know.
- (Mimi hear)
- Hayley: Doug did not turn up in the pub.
- Frank: What you doing in the pub.
- Hayley: We was having drink, I wait for him about 15 mintues.
- Hayley: And...
- (Frank saw blood)
- Hayley: He just....
- Frank: Hold on, something is not right.
- Hayley: What.
- Frank: Why is a blood on the floor
- Hayley: Yeah.
- (Frank hold the gun)
- Frank: Shhhh.
- Frank: This is Detective Nightingale.
- Emma: Frank...
- (Emma groan)
- Frank: Open the door.
- (Hayley open the door)
- (Doug's body)
- Hayley: Doug.
- (Hayley run to Doug's body)
- Hayley: Doug, Doug, DOUG.
- Hayley: He is dead.
- (Emma breath)
- Frank: Emma.
- (Frank run and found Emma's body)
- Frank: Emma.
- Frank: Hayley, I found Emma.
- Hayley: What she doing here.
- Frank: I think she found the body first.
- Hayley: Call the ambulance.
- Frank: Emma, Emma, who did this to you.
- Emma (groan): A killer.
- Frank: Which one, Mimi Mone or Lauren Malloy.
- Hayley: I think she is getting worse.
- Frank: Where that fucking ambulance.
- Hayley: They are coming.
Valerie Michaels-She is attacked and stabbed in the back as she is crawling away she is stabbed in the back of her head. (Mimi)
Perry Johnson-He has his throat slashed (Lauren)
Carly Nelsen-She is stabbed in the heart and in the forehead. (Mimi)
Doug Henson-He is stabbed by Mimi 8 times, she then moves his body to Frank's basement. Emma finds Doug's body then she was stab in the hip and attacked by Mimi,then Lauren attacks both Mimi and Emma.Mimi wakes up and is about to kill a knocked out Emma but she hears Frank and Hayley open Frank's basement door and Frank calls out to Doug.She sneaks out the basement door right as Frank and Hayley are coming downstairs Hayley sees Doug's body and Frank sees Emma hurt on the floor he checks on her and calls for an ambulance.(Mimi)
Jerry Clooney-He is attacked along with Frank and Emma when they was in the hospital. Jerry has his head rammed in to the wall then the killer then knocks TV off the wall and it falls on him crushing his head. (Lauren)
Cynthia Hudson-She is shot by an unmasked Mimi who was pretending to be Cami.
Jonas King-He is killed by an unmasked Lauren she needs money she also steals his white van.
Mimi Mone-She shot by Dennis in the chest when she tries to kill his daughter Caroline, as he is checking on Caroline Mimi gets back up again but she is then shot in the head. Dennis tells the shooter he is a cop and for them to drop the gun and show themselves, he is stunned to see that the shooter is his ex wife and Caroline's mother the supposely dead Natalie Carmen!
Dennis, Natalie, and Caroline go outside and see Sidney, Sam, Debbie, Thomas, Hayley, Cami, Kirby, Frank, Emma, Robert, Roy, Lloyd, Brooke, and Brianna who were also surprised to see that Natalie was alive. Sidney thought that Tatum killed her, Natalie told Sidney that she never fails her mission. Brianna was happy that everything was back to normal, Emma and Hayley are walking back to Emma's car when suddenly a whilte vans pulls up the driver points a gun at them and tells them to get in the back the driver is revealed to be Lauren Malloy! Dennis and Frank see this and take off after the van Lauren leads them on a wild chase through Woodsboro it finally ends when Dennis and Frank shoot at the van hitting the tires and causing it to flip 5 times.Lauren crawls out of the van and get up she is about to shoot Frank but someone grabs her hand and takes the gun it's Brianna who then takes out her voicechanger which she used to torment her victims before she killed them and says hello Lauren! Frank and Dennis go see Emma and Hayley who are shaken up but okay, Frank then arrests Lauren. The judge sends Lauren to a mental hospital while she waits to stand trial for all her murders. Jill Roberts gets some movements back in her legs and she plots her next move.