In the ongoing struggle between humans and alien-human hybrids, a genetic flaw in the hybrids gives humans a temporary advantage. However, when Sara, the daughter of Eve, is born, she grows into the most genetically perfect alien form yet, threatening to shift the balance of power. A team of elite soldiers, led by Dean, is tasked with stopping her from reproducing and spreading her species. As Sara searches for a suitable mate, she leaves a trail of deaths in her wake, putting Dean in a moral dilemma. Meanwhile, Dr. Abbot secretly studies Sara to create an invincible alien race, but his ambition is complicated by Amelia's desperate attempts to survive. The battle for supremacy reaches its peak as the species clash in a deadly confrontation.

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Some movies that have similar genres and were produced around the same time as Species III include Deep Blue Sea, Pandorum, Aliens vs. Predator: Requiem, Beneath Loch Ness, Unearthed, Gabriel.