Sabina Wilson (Kristen Stewart), Elena Houghlin (Naomi Scott), and Jane Kano (Ella Balinska) are working for the mysterious Charles Townsend (Robert Clotworthy), whose security and investigative agency has expanded internationally. With the world's smartest, bravest, and most highly trained women all over the globe, there are now teams of Angels guided by multiple Bosleys taking on the toughest jobs everywhere.

Plot Synopsis:
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The film opens in Rio De Janeiro, Brazil where Sabina Wilson (Kristen Stewart) is flirting with her mark, Jonny Smith (Chris Pang). He makes sexist remarks about women, which leads to Sabina slowly showing him her skills by subduing him with the curtains. Before his bodyguards get her, Sabina is joined by fellow Angel Jane Kano (Ella Balinska). They proceed to fight the goons before they are met by John Bosley (Patrick Stewart), who commends them on their work. After getting all their info on Smith, Sabina and Jane depart with other Angels.

Tech developer Elena Houghlin (Naomi Scott) meets with her boss, Peter Fleming (Nat Faxon), to talk about their newest creation, Callisto, which is meant to revolutionize the power industry but also has a dangerous glitch. Elena wants to bring this to Alexander Brock (Sam Claflin), the CEO of Brok Industries where they work, but Fleming would rather slide it under the rug. After he dismisses Elena, his secretary Ingrid (Hannah Hoekstra) picks up a card for Elena with the Angels' logo.

John meets with Rebekah "Boz" Bosley (Elizabeth Banks), as well as the other group of Bosleys to celebrate John's retirement from the Townsend Agency, as he is the longest-working Bosley and oldest friend of "Charlie". He gets one last call from the man himself wishing him luck and thanking him for his service.

In Hamburg, Elena and her assistant Langston (Noah Centineo) join Fleming in presenting Callisto to Brock. It is set to provide clean energy and link up to other appliances, which would put Brok Industries high up in the energy business. Brock is impressed with their work, but it doesn't stop him and Fleming from undermining Elena's work.

Edgar Bosley (Djimon Hounsou) brings Sabina and Jane together for an assignment to track Elena. She meets Edgar in a cafe where she tells him about Callisto and how she plans to expose her bosses for trying to put it out while knowing the risks it may cause. While Sabina and Jane keep an eye on her, an assassin named Hodak (Jonathan Tucker) lurks. Edgar notices him and tries to warn Elena, but Hodak proceeds to attack. Edgar and the Angels spring into action and get Elena out of the cafe. Jane fights Hodak briefly before she and Edgar take Elena in a van. Hodak pursues and fires with a machine gun, and Jane hits back with her own rifle. He hits Edgar in the neck and causes the van to fall into the river. Edgar dies, but Jane frees Elena. Before Hodak can kill them, Sabina trips him with her motorcycle, but he sets an explosion that allows him to get away.

Boz picks the ladies up. Elena is freaked out while Jane is quietly devastated by Edgar's death and now wants revenge against Hodak. They take Elena to a safe house to explain that Hodak was targeting her because someone doesn't want her to blow the lid off Callisto, which can be weaponized to trigger EMP's that cause brain aneurysms. The team plans to infiltrate Brok Industries to acquire Callisto's prototypes before any of the villains try to get their hands on it.

The ladies show up with the same hairstyles to confuse surveillance cameras and other Brok employees. Jane manages to get into the lab, but they find that Callisto is not where Elena thought it would be. They eventually find it, and Elena uses it to try and disable the power so they can get past security. Unforuntately, one unlucky guard stands in the way and suffers a fatal seizure when the trigger goes off. Boz gets the team out of there. It is then shown that Brock has been observing the whole scene and is dismayed that Elena is still alive.

Boz brings the ladies to the Berlin outpost of the agency to meet with The Saint (Luis Gerardo Mendez), who provides them with a place to stay, and also sets up a small feast in honor of Edgar. The team then reviews their data to find that Fleming is the one who took the other Callisto prototypes. They track him to Istanbul and make plans to find him there. Later, Boz meets with an unseen figure to let her know about Istanbul, and she asks what they do with Elena.

The Saint equips the team with gadgets as they head to Istanbul. In order to find out where Fleming is planning to sell off Callisto, Jane gets help from a woman from her past named Fatima (Marie-Lou Sellem), who used to take care of Jane but was hurt by her after she left without a word. Fatima relents and helps her, which leads the team to find Fleming and follow him. Boz learns he plans to sell Callisto the next day at the Turkish Derby. The team heads to the Derby that day to keep an eye on Fleming, following him to a rock quarry. They discover that Fleming is selling to Smith, with Hodak present for the meeting. Smith asks for a demonstration, but when Fleming finds it too risky to pull off safely, Hodak shoots him in the head. The team is compromised, and they must fight off the other assassins. Smith and Hodak get away, and Boz is also gone as the ladies try calling her for help.

The ladies return to the safe house where they suspect Boz might be a mole in the agency. Elena gets a call from John warning them to get out of there. An explosion goes off and forces them to run. Elena is found outside by Boz, who appears to be aiming her gun at her, but she is shot down by John. He takes Elena with him for safety.

Sabina recovers from her injuries, with Jane worrying by her side. The Saint brings Boz in, and she clears the air about what the team thinks of her. She had to leave because she knew John was the real traitor, and since she has tracked him and found out he was in Istanbul, she had to find him before he got to the other ladies. They realize Elena is in danger, and Boz states that John is trying to establish his own network of criminals after being passed over to succeed Charlie. They plan to sneak into a party that Brock is throwing for his investors to present Callisto.

Elena learns that John is the bad guy and is ordered by him to program Callisto to his needs. When she refuses, he shows her that he is keeping Langston as a hostage. Sabina and Jane get in dressed as party guests. Brock and Hodak meet with John, where John reveals to Brock that he is not the one in control as he thought. John forces Elena to reprogram Callisto for his use and then tries to trigger the EMP to kill her and Langston. After he leaves, Elena frees herself and Langston. Sabina and Jane find Hodak and fight him. Jane takes him one-on-one and throws him over the balcony where he is impaled on an ice sculpture. The team then stands off against John and his men, but Boz gets other Angels disguised as party-goers to subdue the henchmen, and Sabina punches John's lights out. Smith is then revealed to be Boz's informant who worked to bring John down. The team then leaves, with Langston following them.

During the end credits, Brock is shown to be arrested. Elena is officially recruited as an Angel by classic Angel Kelly Garrett (Jaclyn Smith), who has been using a voice simulator to speak as Charlie. Elena is trained by multiple instructors (Danica Patrick, Ronda Rousey, Laverne Cox) and joins other recruits (Hailee Steinfeld, Lili Reinhart, Aly Raisman, Chloe Kim) in an air jump, but Boz tells her to land the plane. Elena does so safely and rejoins Sabina and Jane.

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