Courteney Cox was the first cast member to sign up to return as Gale Weathers. She stated that she did not hesitate to return because she loved playing Gale, and jokingly said that she'd even play her for free.
There were no props left over from the previous films -- "Not even the graphics files from the posters and book covers," according to production designer Michèle Laliberté -- so everything for the shrine had to be recreated from scratch. Laliberté told IndieWire, "We went through the films and made a list of all the murders and all the victims," adding that everything had to be from the murders that occurred in the Scream movies, not the Stab movies, and that "the only Stab objects were related to Scream 3, which was about the making of a Stab movie."
Neve Campbell stated on June 6, 2022, that she would not be reprising her role of Sidney Prescott, after starring in the five previous entries, due to a salary dispute with Paramount. Campbell's statement read, "As a woman I have had to work extremely hard in my career to establish my value, especially when it comes to Scream. I felt the offer that was presented to me did not equate to the value I have brought to the franchise. It's been a very difficult decision to move on. To all my Scream fans, I love you. You've always been so incredibly supportive to me. I'm forever grateful to you and to what this franchise has given me over the past 25 years." After Campbell announced that she wouldn't be reprising her role as Sidney, her former Scream co-star Matthew Lillard offered his support for her decision. "Did Tom Cruise take less money for Maverick 5 [sic]?" he asked, insisting that a woman should not be expected to take a smaller paycheck. He noted that Scream V was a "smash hit," and that Campbell should be paid accordingly.
Courteney Cox has now portrayed Gale Weathers in six installments of this franchise, all with theatrical distribution, released across four decades. This is a record for any actress, a feat she only shares with Milla Jovovich, who appeared in all six Resident Evil films before the reboot.
Somebody dressed as Mojo Jojo from Powerpuff Girls (1998) is seen in the subway. Roger Jackson, the voice of Ghostface, is also the voice of Mojo Jojo.