Andy Sachs returns to Runway as Miranda Priestly navigates a new media landscape and Runway's position within. The duo reconnect with former assistant Emily Charlton, now the head of a luxury brand that possesses funding which could ensure Runway's survival.
| Actor | Role |
|---|---|
 Anne HathawayAndy | Andy |
 Meryl StreepMiranda | Miranda |
 Emily BluntEmily | Emily |
 Stanley TucciNigel | Nigel |
 Kenneth BranaghStuart | Stuart |
 Justin TherouxBenji | Benji |
 Lady GagaLady Gaga | Lady Gaga |
 Lucy LiuSasha | Sasha |
 Tracie ThomsLily | Lily |
 Tibor FeldmanIrv | Irv |
 B.J. NovakJay | Jay |
 Patrick BrammallPeter | Peter |
 Simone AshleyAmari | Amari |
 Caleb HearonCharlie | Charlie |
 Helen J. ShenJin | Jin |
 Rachel BloomTalia | Talia |
 Larry MitchellMack | Mack |
 George C. WolfePaul | Paul |
 Daniel LiuDirk | Dirk |
 Pauline ChalametIlana | Ilana |
 Bria CondonMarta | Marta |
 Esco JouléyJenny | Jenny |
| RRishi MukherjeeSandeep | Sandeep |
 Wes McGeeFrank | Frank |
| EEloise RoBronwyn | Bronwyn |
| TTanya HutchisonFlight Attendant | Flight Attendant |
 Briga HeelanPassenger | Passenger |
 Andrea LogiudiceAndrea Logiudice Agnesina | Andrea Logiudice Agnesina |
| JJulia Ty GoldbergNew Second Assistant | New Second Assistant |
| AAvery BedermanNigel's Assistant | Nigel's Assistant |