After receiving a cryptic, urgent distress call from Dr. Beverly Crusher, Admiral Jean-Luc Picard enlists help from generations old and new to embark on one final adventure: a daring mission that will change Starfleet, and his old crew forever.

Patrick Stewart (Admiral Jean-Luc Picard)
Jeri Ryan (Commander Seven of Nine)
Michelle Hurd (Commander Raffi Musiker)
Ed Speleers (Jack Crusher)

Jonathan Frakes (Captain William T. Riker)
Gates McFadden (Dr. Beverly Crusher)

Orla Brady (Laris)
Todd Stashwick (Captain Liam Shaw)
Ashlei Sharpe Chestnut (Ensign Sidney La Forge)
Anthony Azizi (Orion Drug Dealer)

Stephanie Czajkowski (Lieutenant T'Veen)
Joseph Lee (Lt. Matthew Arliss Mura)
Chad Lindberg (Ensign Eli Foster)
Jin Maley (Ensign Kova Rin Esmar)
Jani Wang (Bartender)
Christian Crandall (Dark Haired Man)
Amy Earhart (S.S. Eleos Computer)
Grace Lee (Picard Château/La Sirena Computer)
Ric Sarabia (Human Patron)

• This is Beverly Crusher's first live action appearance since Star Trek: Nemesis, though she did appear in animated holodeck form in the Star Trek: Prodigy episode "Kobayashi".
  
• Seven of Nine is now in Starfleet, with a rank of Commander. She is first officer of the U.S.S. Titan NCC-80102-A. The Titan-A is a refit, Neo-Constitution class.
  
• Liam Shaw has been the commanding officer of the Titan for the last five years, following Riker's retirement. He seems rather antagonistic towards Seven, ordering her to use "Commander Hansen" instead of Seven of Nine, and pointedly mentions her (and Picard's) status as former Borg.
  
• Dr. Crusher's ship is the S.S. Eleos XII NAR-59019, a Phoenix-class medical rapid response starship. Crusher has not seen any of the other Enterprise crew members in twenty years, when she cut off contact for unknown reasons.
  
• Raffi is now working for Starfleet Intelligence and is investigating the theft of an experimental weapon from a Daystrom Institute station. She determines the Rachel Garrett statue on M'talas Prime is "The Red Lady" clue she gathered from the Orion drug dealer. She arrives in time to see the Starfleet recruitment center obliterated by the weapon.
  
• There are several references to the upcoming Frontier Day, celebrating the 250th anniversary of Starfleet.
  
• Ensign Sidney La Forge is Geordi's daughter. She is the helmsman of the Titan.
  
• The U.S.S. Titan bridge officers were given full names on social media: Lt. Matthew Arliss Mura (Joseph Lee) and Ensign Kova Rin Esmar (Jin Maley).
  
• Instead of an opening title sequence, there is only a Star Trek Picard title card with a musical cue from Star Trek: First Contact.
  
• The end credits includes a dediction "For Annie". Annie Wersching played the Borg Queen in Season 2 and she passed away in January 2023.
  
• The character Ed Speleers plays is revealed to be Dr. Crusher's son…