A rare mutation has occurred within the vampire community - The Reaper. A vampire so consumed with an insatiable bloodlust that they prey on vampires as well as humans, transforming victims who are unlucky enough to survive into Reapers themselves. Blade is asked by the Vampire Nation for his help in preventing a nightmare plague that would wipe out both humans and vampires.

In the final days of World War II, the Nazis attempt to use black magic to aid their dying cause. The Allies raid the camp where the ceremony is taking place, but not before they summon a baby demon who is rescued by Allied forces and dubbed "Hellboy". Sixty years later, Hellboy serves the cause of good rather than evil as an agent in the Bureau of Paranormal Research & Defense, along with Abe Sapien - a merman with psychic powers, and Liz Sherman - a woman with pyrokinesis, protecting America against dark forces.

Using massive piloted robots to combat the alien threat, earth's survivors take the fight to the invading alien force lurking in the depths of the Pacific Ocean. Nearly defenseless in the face of the relentless enemy, the forces of mankind have no choice but to turn to two unlikely heroes who now stand as earth's final hope against the mounting apocalypse.