- Cassandra Webb is a New York metropolis paramedic who begins to demonstrate signs of clairvoyance. Forced to challenge revelations about her past, she needs to safeguard three young women from a deadly adversary who wants them destroyed.
- In a switch from the typical genre, Madame Web tells the standalone origin story of one of Marvel publishing's most enigmatic heroines. The suspense-driven thriller stars Dakota Johnson as Cassandra Webb, a paramedic in Manhattan who develops the power to see the future... and realizes she can use that insight to change it. Forced to confront revelations about her past, she forges a relationship with three young women bound for powerful destinies...if they can all survive a deadly present.—Sony Pictures
- In the film, the origin story of Cassie Webb (Johnson) is explored as she confronts her past while trying to save three young women (Sweeney, Merced, O'Connor) from Ezekiel Sims (Rahim), who wants to kill them before they become Spider-Women in the future and kill him. Cassandra Webb (Madame Web) is a New York City paramedic who starts to show signs of clairvoyance. Forced to confront revelations about her past, she must protect three young women from a mysterious adversary who wants them dead. Webb realizes that she can use this power to see the future to change it.—tpsimpleman
- In 1973 in the jungles of Peru, a research team led by Ezekiel Sims and his pregnant partner Constance Webb discovers an unidentified species of spider with rare healing properties. Ezekiel betrays the team and claims the spider for himself before leaving Constance for dead. An indigenous tribe attempts to save Constance, but she dies shortly after giving birth to Cassandra.
In 2003, Cassandra, going by "Cassie", works as a paramedic in New York alongside her co-workers Benjamin "Ben" Parker and O'Neil. During a dangerous call, Cassie falls into the water and has a near-death experience. Ben revives her but she begins to experience visions. Initially, she dismisses them as déjà vu, but after failing to prevent O'Neil's death, Cassie realizes that she can see into the future.
Ezekiel, who has limited precognition power and enhanced physical abilities, collects information on three young women: Julia Cornwall, Anya Corazon, and Mattie Franklin. His visions lead him to believe that they are destined to kill him. Cassie is also drawn to the same women and intervenes to stop Ezekiel from ambushing them at Grand Central Station. She steals a taxi and takes Julia, Anya, and Mattie out of the city to hide them in a nearby forest. Cassie returns to her apartment and finds Constance's notes, which reveal Ezekiel's identity and the true nature of his powers. Ignoring Cassie's instructions, the girls go to a diner where Ezekiel finds them. After briefly incapacitating Ezekiel by ramming him with the car, Cassie takes the girls back to Queens and they take refuge in Ben's house.
Cassie flies to Peru and tracks down the tribal chief who saved her mother. The chief puts Cassie through a ritual that separates her soul from her body. She experiences a plane of higher consciousness where all living things are connected and where every possible future can be seen. She learns that Constance sought the spider to save her from a fatal hereditary disease.
Ben's pregnant sister-in-law Mary goes into labor and he takes her to the hospital, along with the girls. Ezekiel intercepts them again, but Cassie rescues the girls in an ambulance and distracts Ezekiel so Ben and Mary can escape. The group lures Ezekiel to a condemned firework factory and sets up traps to disorient him while Cassie calls for a medical evacuation helicopter to fly to their location. Ezekiel destroys the helicopter and separates the girls, then taunts Cassie with Constance's death.
By tapping into the Web of Life, Cassie guides the girls to safety. She sets off the final trap, which fatally crushes Ezekiel. An ignited firework strikes Cassie in the face, blinding her. Cassie is taken to the hospital just as Mary gives birth to her son Peter.
Cassie wakes up to discover that she is now blind and paraplegic due to her injuries. However, her connection to the Web of Life enables her to see fully into the future. Cassie assures the girls that she will mentor them in their future roles when the time comes.
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