In the South Pacific, a translucent alien spaceship hovers over the sea while a test stealth plane piloted by Mercer Alex Reid encounters the craft and gives chase. The plane begins to malfunction, and he lands on a nearby island to inspect the scene. There, he discovers the spacecraft destroyed and its alien pilot slain by a large spider that turns its attention toward Mercer.
Ten months later, Loren Mercer, Joli's sister, is hired to be the pilot of a medical expedition organized by Dr. Samuel Leon José Sancho and assistant Susana Gabriel Neus Asensi, after having received a native from an island who died from an unknown virus. The expedition is led by Lev Valentine Chris Potter, with Bear Rocqueford Allen and Reyes Luis Lorenzo Crespo, arachnologist Henry Capri Ravil Isyanov, native guide Toe Boy Robert Vicencio and two other native helpers. Once they reach the island, the plane begins to malfunction and they are forced to land on the beach.
The next morning, some strange ticks burrow into Reyes. Upon reaching the village, Capri discovers that several insects have mutated. Ticks then start to come out of Reyes and Bear mercy-kills him to end his pain. At night, the group is attacked by a giant centipede, killing one of the natives. Mercer finds some of her brother's clothes and confesses to Valentine that she's looking for her brother. Valentine decides they all are leaving the island next morning, although Mercer and Capri refuse.
Next day, Valentine agrees to help Mercer find Joli once they get everyone off the island but Capri has left the village. Bear is sent with a native to find a radio signal for help but while on a river, the native is killed by a small creature. Capri finds the giant centipede dying and the giant spider attacks him. The rest of the group find the remains of Joli stuck in a tree. Then they find Capri trapped in spider web and bitten by it, he deduces that there's a giant alien spider trying to breed. Capri asks to be killed and Susana does so. The spider reaches them and they flee. While doing so, Susana is trapped in spider webs and she escapes thanks to Mercer and Valentine. Samuel is caught by the spider and kills him by throwing acid to his face.
The three enter a military bunker after Toe Boy disappears. The spider attacks through one of the windows and Valentine attacks back, getting cut by one of its fangs. Mercer shoots the spider in an eye and it flees. At night, the spider sneaks through the bunker's roof and they lock in a small room. Susana, suffering from claustrophobia, opens the door and gets killed with its stinger. After cutting one of its legs with the door, they escape through a trapdoor to underground tunnels. Outside they fall asleep and Mercer has a nightmare. Next morning, Bear and Toe Boy find them and they try to kill the spider.
In the tunnels, a weak Valentine stays behind. They find the spider breeding in a silk cocoon over a spider egg sac. Mercer plans to knock the spider down and have Bear shoot it but it wakes early and kills Bear. Mercer throws Toe Boy's vial of black widow poison to the spider's face, hurting it. The spider chases Mercer but, as she stumbles, it traps her in spider web. When it is about to kill her, Valentine appears shooting at it while Toe Boy throws poisoned darts. As it tries to flee, Mercer pulls the spider web thread to drop from the ceiling onto a stalagmite, killing it. As they walk the jungle, another giant spider watches them from an overhead cliff.
