Scream 20 takes place after Scream 19, Fifi's body is still mssing, and her older brother and sister come back to Maryland to hold a memorial service for her. Hayley's evil twin sister Lauren is still alive. Also another Ghostface killer is after Sidney Prescott.
- Keanu Reeves as Thomas Connor
- Georgie Henley as Hayley McDonald/Lauren Malloy
- Neve Campbell as Sidney Prescott
- Bradley Cooper as Clint Altieri
- Matthew Lillard as Det Sam Macher
- Amber Heard as Jessica Mitchell
- Matthew Knight as Ethan Carsia
- Kyle Lowder as Mike Mone
- Ashley Roberts as Samantha Mone
- Billy Burke as Rev Pete Maloney
- Amy Davidson as Pauline Massey
- Justin Berfield as Joey Kerns
- Teri Polo as Evelyn Maloney
- Kate Mara as Nancy Rogers
- Brad Dourif as Kevin Gibbs
- Lauren Malloy-She wasn't dead only in a coma she woke up killed her doctor and is continuing her killing spree.
- Mike Mone-He blames his sister Sally for their younger sister Fifi becoming a killer but he can't do anything about her since she is dead he wants to kill her twin Samantha.
- Clint Altieri-He is Mickey's younger brother and he is obsessed with killing Sidney Prescott only.
Det Sam Macher
- Nancy Rogers -She is knocked out then hung from a tree in the woods. (Mike)
- Kevin Gibbs -He is attacked from behind and stabbed in the back the killer continues to stab him as he tries to crawl away. (Lauren)
- Pauline Massey -Sidney's friend she is tied to a chair and tortured she is then stabbed to death. (Clint)
- Joey Kerns -He is attacked as he is walking home and dragged behind the bushes and gutted (Lauren and Clint)
- Rev Pete Maloney - He is killed a few hours after Fifi's Memorial service he is stabbed in the forehead. (Mike)
- Evelyn Maloney -She is stabbed in the heart. (Lauren)
- Samantha Mone -An unmasked Mike shoots his sister to death.
- Mike Mone- He committs suicide after he kills Samantha.
- Clint Altieri -He is stabbed by Sidney and then shot by Sam Macher 5 times after he gets up like Mickey did and tried to go after her again.
- Lauren Malloy -She is stabbed by Hayley when they are fighting.
Sidney had no idea that Mickey had a younger brother he never talked about his family with Derek when they were at Windsor 14 years ago.She also felt awful about the Mones they were a troubled family and now they were all dead.A day later 2 teenagers were walking near a creek when they saw a young woman with long blonde hair laying on the ground they went to look at her thinking maybe she was dead but she wasn't she opened her eyes and looked at them they told her not to worry they were going to get help for her the young woman said thank you it was Fifi Mone!