NOTE: This spoiler was submitted by Jeremy

Los Angeles, 2028 - A deadly riot has broken out over the city. Four thieves, led by Sherman (Sterling K. Brown), take advantage of the chaos by robbing a bank. They have to flee before they can open the vault, but Sherman's brother (Brian Tyree Henry) steals what appears to be an ordinary pen from a teller. After blowing a hole through the wall to escape, they are found by four armed officers who exchange fire with the crooks. One of them is killed, Buke (Kenneth Choi) gets shot in the neck, and Sherman's brother is shot multiple times before they kill the guards. Sherman grabs his brother and heads to get help.

The thieves go to Hotel Artemis, a secret hospital for criminals run by Nurse Jean Thomas (Jodie Foster). Sherman and his brother scan their wrists with their membership chips implanted, but Buke is denied because his won't scan. After cursing out Jean for this, she brings in her large assistant Everest (Dave Bautista) to take Buke outside. Buke tries to fight Everest, but he overpowers him and forces him to stay outside as the riots are getting closer.

Jean tends to Sherman and his brother, giving them the respective code names of Waikiki and Honolulu. She treats their wounds and also tries to replace Honolulu's liver after it has sustained severe damage. He is put on life support.

In other parts of the hotel are Acapulco (Charlie Day), an arms dealer who is there because someone tried to rip his face off, and Nice (Sofia Boutella), an assassin who purposely hurt herself to get close to a target. He tries to intimidate her until Waikiki, who has something of a history with Nice, intervenes. Acapulco tries to be a tough guy and threaten Waikiki, but neither of them are buying it from him.

Jean receives a call from a man named Crosby Franklin (Zachary Quinto), who demands that she treat his father, the owner of the hotel. He and his goons are on their way with the man in order for him to get medical assistance. Meanwhile, the power grid continues to go out as a result of the authorities handling the riots, so Everest has to keep switching the power back on.

As the riots are growing more intense and violent, a cop named Morgan (Jenny Slate) is outside the hotel calling for Jean and begging for help, addressing her as Mrs. Thomas. Everest tries to talk Jean against letting her in, but she feels she might know Morgan. Jean grabs a framed photo of a little boy and brings it outside to show to Morgan, who identifies the child as Beau. As they try to pull Morgan inside, a couple of punks try to steal Jean's bag, but she tries to give them a few valuables. The punks are then shot by armed officers who attempt to go after Jean until Everest shows up and beats them all to death.

Jean treats Morgan's wounds, and we learn that Beau was Jean's son who supposedly died from an overdose as a young man. After she gets better, Morgan leaves the hotel.

Waikiki chats with Nice, and she reveals to him that the pen that Honolulu took is actually a portable vault containing yellow diamonds valued at $18 million that belong to a notorious criminal called The Wolf King (Jeff Goldblum). Waikiki takes the pen to his brother and shows him what's inside. He wants both of them to leave, but Honolulu is still on life support, so he says he is okay if Waikiki leaves without him. Waikiki then uses a 3D printer to make himself a gun, despite the rules against having a weapon in the building.

The Wolf King and his goons arrive with Crosby and his own gang. Wolf King has an injury that needs treatment, so Jean reluctantly treats him. After fixing his wound, Wolf King reveals that he had Beau killed after he stole a car from him. Jean considers killing him in retribution, but killing patients is against the rules of the Artemis.

Knowing that Wolf King is in the hotel and since he is a target for her employer, Nice kills the power at the hotel just as Acapulco is trying to catch a helicopter ride out of there. This causes Honolulu's life support to go out, and Jean cannot save him, so he dies. Acapulco's ride then flies away due to potentially being compromised. Nice finds Wolf King's room and slits his throat with a broken piece of glass. She confirms the kill to her employer using a recorder implanted in her eye. Moments later, she runs into Waikiki, who knows what she did, although she expresses remorse for Honolulu's death. Acapulco then shoots Waikiki and nearly goes for Nice until Waikiki fights him and sticks Acapulco's head in the 3D printer, which impales his head and kills him.

Nice goes to fend off Wolf King's guys, as does Everest. Waikiki and Jean attempt to escape the hotel until they are found by Crosby, who has found out his father has died. Crosby attacks Waikiki, until Jean throws him medical sealant that he uses to blind Crosby, and then Jean kills him by injecting him with baby elephant tranquilizer.

Waikiki and Jean make their way out, but Jean decides she has to stay to help others now that Wolf King and Crosby are dead. Waikiki parts with her on good terms before he heads off to Vegas to a different hotel called The Apache. Everest, having survived his encounter with Wolf King's mob, turns the lights back on at the Artemis, and Jean heads back inside.

The mid-credits scene show that Nice has also apparently survived as she runs through the shadows.

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In 2028 Los Angeles, violent riots have plagued the city. A criminal hospital called Hotel Artemis hosts killers and dealers, including two bank robber brothers, codenamed Waikiki and Honolulu. Honolulu unknowingly stole a pen that is actually a vault containing valuable yellow diamonds that belong to a notorious criminal called The Wolf King, and he and his son Crosby are on their way to the hotel for Wolf King to get medical treatment.

Nurse Jean Thomas runs the place with her huge assistant Everest. An assassin named Nice is there to target Wolf King. He arrives and reveals that he killed Jean's son after he stole a car from him. Before Jean can kill him, Nice kills the power to the hotel, which causes Honolulu's life support to go off and kill him, but she uses it as an opportunity to kill Wolf King. She and Everest hold off Wolf King's goons while Waikiki and Jean try to escape. Crosby attacks them but they kill him too. Jean decides to stay at the hotel while Waikiki escapes, and Everest manages to get the power back on.

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