Full story
In 1973, in the Peruvian Amazon, pregnant researcher Constance Webb finds a rare spider with healing powers. The expedition's guard, Ezekiel Sims, betrays her, shoots her and steals the spider. A local tribe tied to the spiders tries to save her. Constance dies, but her baby, Cassandra, survives.
In 2003, Cassie Webb is a paramedic in New York who works with Ben Parker, whose sister-in-law, Mary Parker, is pregnant. During a rescue, Cassie goes into a river with a car and is clinically dead for a moment. After that, she starts having visions and realizes she's seeing moments before they happen. Ezekiel, meanwhile, has gotten rich and picked up spider powers from the stolen venom. He has nightmares in which three women in spider suits kill him in the future, and he decides to wipe them out while they're still teenagers.
The girls are Julia Cornwall, Anya Corazón and Mattie Franklin. On a train, Cassie has a vision of Ezekiel killing them and acts first, getting the girls out of the car. From then on she becomes their protector, even though she has no idea how to look after anyone. With help from an agent he's bought, Ezekiel tracks the group and strikes again. Cassie finds her mother's notes and learns who he is.
Leaving the girls in hiding, Cassie travels to Peru. There she meets Santiago, a tribe member who knew Constance. He explains that her mother was looking for the spider to cure her daughter's illness, and that the bite passed a gift to Cassie: she can see the future and act inside it. Cassie learns to control the visions. While she's away, the girls go out to a diner and Ezekiel finds them. Cassie gets back in time to save them.
The final showdown is at an abandoned fireworks factory. Cassie and the girls set traps. Using her visions, Cassie anticipates Ezekiel's every move and leads him under a giant sign that comes crashing down and kills him. Cassie is badly hurt in an explosion. At the hospital, Mary Parker gives birth to a boy named Peter. Cassie wakes up blind and unable to walk, but with her visions clearer than ever. She promises the three girls she'll prepare them for what they're meant to become, and the film ends on a vision of them as spider-women.