Taxi driver Jack Bruno (Dwayne Johnson) unintentionally becomes protector and ally to two extraterrestrial siblings, Sara and Seth, who possess telekinetic/telepathic powers and seek to reach Witch Mountain to escape government agents and a ruthless private-sector operative. The film follows high-speed chases, government pursuit, and a race to prevent the villains from exploiting the children's powers.

: The character of Dr. Alex Friedman (Carla Gugino), a discredited astrophysicist, represents the tension between hard science and fringe beliefs. Her character validates those who are often mocked for their convictions, transforming "discredited" theories into life-saving reality.

: They are relentlessly hunted by Henry Burke ( Ciarán Hinds ), the leader of a secret government organization known as "Project Moonquill," and a "Siphon," an advanced alien bounty hunter sent to stop the children at all costs.