 | Tom Holland als Nathan Drake |
 | Mark Wahlberg als Victor 'Sully' Sullivan |
 | Sophia Ali als Chloe Frazer |
 | Tati Gabrielle als Jo Braddock |
 | Antonio Banderas als Santiago Moncada |
 | Steven Waddington als The Scotsman |
 | Rudy Pankow als Sam Drake |
 | Tiernan Jones als Young Nathan Drake |
 | Pingi Moli als Hugo |
 | Jesús Evita als Guard at Museum |
 | Georgia Goodman als Sister Bernadette |
 | Diarmaid Murtagh als Police Officer |
 | Joseph Balderrama als Carlos |
| Serena Posadino als Goldie |
 | Alana Boden als Zoe |
| Jonathan Failla als Unsuspecting Doorman |
 | Anthony Thomas als Luxury Sedan Driver |
| Peter Seaton-Clark als Auctioneer |
 | Robert Maaser als Guard at Auction |
 | Eskindir Tesfay als Security Guard |
 | Manuel de Blas als Armando Moncada |
 | Carme Capdet als Spanish Nun |
| Julia Schunevitsch als Club Bartender #1 |
| Alois Knapps als Club Bartender #2 |
 | Patricia Meeden als Spanish Woman in Club |
 | Nolan North als Hotel Guest |
| Matt Barkley als Hotel Bellman |
 | Pilou Asbæk als Gage |
| Jimmy Hart als Concepcion Helo Pilot |
 | Brett Praed als Concepcion Co-Pilot |
 | Carlo Kitzlinger als Trinidad Helo PIlot |
 | Rubén Doblas Gundersen als Young Man (uncredited) |
| Denise Chamian | Casting |
| Charles Roven | Producer |
| Chris Lebenzon | Editor |
| John Papsidera | Casting |
| Manfred Banach | Sound Mixer |
| Marlene Stewart | Costume Design |
| Shepherd Frankel | Production Design |
| Avi Arad | Producer |
| Richard Pearson | Editor |
| Jeong Jeong-hun | Director of Photography |
| Cornelia Ott | Art Direction |
| Elli Griff | Set Decoration |
| Kami Asgar | Supervising Sound Editor |
| Art Marcum | Screenplay |
| Art Marcum | Executive Producer |
| Matt Holloway | Screenplay |
| Matt Holloway | Executive Producer |
| Ramin Djawadi | Original Music Composer |
| Alex Gartner | Producer |
| Mark DeSimone | ADR Mixer |
| Ruben Fleischer | Director |
| Ruben Fleischer | Executive Producer |
| Allan A. Apone | Makeup Artist |
| Beau Borders | Sound Re-Recording Mixer |
| Ari Arad | Producer |
| Nenad Pečur | Art Direction |
| Brad Shield | Second Unit Director of Photography |
| Chas Jarrett | Visual Effects Supervisor |
| Carter Swan | Executive Producer |
| Tom Holland | Executive Producer |
| Rafe Judkins | Screenplay |
| Rafe Judkins | Screenstory |
| David Bernad | Executive Producer |
| Daniel Chour | Art Direction |
| Neil Druckmann | Executive Producer |
| Michael Fissneider | Art Direction |
| Clay Enos | Still Photographer |
| Erin Oakley | Supervising Sound Editor |
| Stefan Speth | Art Direction |
| Adam De Coster | Foley Artist |
| Bob Dohrmann | Executive Producer |
| Rachael Speke | Makeup Artist |
| Florian Müller | Art Direction |
| Matt Cavanaugh | Sound Effects Editor |
| Nebojša Tabački | Set Designer |
| Gabe Hilfer | Music Supervisor |
| Calla Klessig | Art Direction |
| Thomas Elder-Groebe | Visual Effects Producer |
| Evan Wells | Executive Producer |
| Mark D. Walker | Screenstory |
| Edwin Rivera | Visual Effects Supervisor |
| Petra Ringleb | Set Designer |
| Asad Qizilbash | Executive Producer |
| Margarethe Przywara | Costume Supervisor |
| Shrijeet Modi | Visual Effects |
| Ana Saric | Set Designer |
| Jon Hanley Rosenberg | Screenstory |
| Wilko Drews | Set Designer |
| Tara Mason | VFX Artist |
| Mathias Datow | Assistant Director |
| David Ingram | Supervising Art Director |
| Frédéric Gaudin | VFX Artist |
| Alejandro Cymerman | Art Direction |
| Patricia Woerler | Art Direction |
| Julian Burger | Set Designer |
| Penélope Gómez | Set Dresser |
| Christian Meinherz | Set Dresser |
| Jordan J. Melo | Set Dresser |
| Florian Radloff | Set Dresser |
| Prithvi Parmar | VFX Artist |
| Laila Alsane | Assistant Makeup Artist |
