Developed at Umbrella Europe's Sixth Laboratory, the Nemesis was intended to prove that it was possible for T-virus infected creatures to retain most of their intelligence. A specifically engineered parasitic organism called an NE-α parasite was introduced into the body of a typical 103 series Tyrant, which would infest the host's brain stem and function as a secondary brain to replace the original that had been rendered useless after the initial Tyrant engineering process. The parasite would cause further mutation of the subject's body, resulting in increased muscle mass and the growth of tentacle-like appendages in its body.
Umbrella deployed the Nemesis in September 1998, in the American mid-western town of Raccoon City that was currently suffering a T-virus outbreak caused by an incident in Umbrella's underground research facility. The creature's mission was to find and kill all surviving members of the Special Tactics and Rescue Squad (S.T.A.R.S.), who had witnessed Umbrella's illegal genetic research and now posed a threat to the company. Programmed with information on the S.T.A.R.S.'s identities and equipped with heavy weaponry, the Nemesis was air-dropped into the dying city and began seeking its quarry. It encountered Brad Vickers and Jill Valentine - the last two S.T.A.R.S. in the city - outside the Raccoon Police Department. It killed Brad by impaling him in the face with its tentacle and then proceeded to hunt Jill. Jill would elude the Nemesis temporarily but the creature would always manage to track her down.
During an encounter at the Michael Bell clock tower, a rescue chopper flew in to retrieve Jill and fellow survivor, UBCS grunt Carlos Oliveira. Recognizing that its target would be able to escape, Nemesis wielded a rocket launcher and used it to shoot down the chopper, stopping Jill from escaping. It then attacked her and managed to injure her with its tentacle, infecting her with the T-virus in the process. Carlos managed to inflict heavy damage on the creature by shooting its rocket launcher, causing it to explode. The damaged Nemesis retreated in order to repair itself. It reappeared days later, after Jill had been cured thanks to a T-virus vaccine Carlos had acquired from Raccoon General Hospital. It cornered Jill inside Umbrella's abandoned Dead Factory facility, where failed experiments and waste materials were sent for destruction. By then, Nemesis had lost its limiter coat and had undergone a slight mutation. It fought Jill inside the waste disposal facility but was seemingly destroyed after having acid sprayed over it and having its head blown off by Magnum fire.
This was not the end for it yet, however. As Jill and Carlos passed through a weapon testing area inside the factory, the Nemesis crawled in after them. It had mutated into a horrific mass of boiled flesh with a maw filled with spiked teeth and grew to titanic proportions. It progressed toward its target slowly, its shear mass slowing it down, and spewed acidic toxins from its tentacles. Jill was finally able to destroy the Nemesis by activating a large rail gun weapon inside the room, and with it, blew the Nemesis into bloody scraps.
- Intelligence - While not as intelligent as a normal human, the Nemesis is capable of analyzing a situation and determining the best course of action. It has a greater sense of self-preservation than other B.O.W.'s and knows when it needs to retreat. It can analyze its enemies' actions and thus prioritize its targets.
- Weaponry - The Nemesis's enhanced intelligence allows it to wield various types of weaponry such as knives and handguns. When deployed in Raccoon City, it had access to heavy weapons that normal human soldiers would not be able to carry. In Resident Evil 3: Nemesis, it carries a rocket launcher in several of its encounters with Jill. In Operation Raccoon City, it uses a gatling gun as it fights off special ops and USS troops.
- Tentacles - Nemesis can use its parasitic tentacles to choke, whip or even impale enemies. Because the T-virus runs through its body, being wounded by its tentacle can result in infection and eventual zombification.
- Superior Strength - Nemesis is capable of great feats of strength, such as charging through walls or throwing vehicles. Its enhanced muscle tissue can absorb most impacts, allowing it to shrug off gunfire easily. The coat it wears is also bulletproof and provides extra protection, as well as limiting its power and preventing it from mutating out of control.
- Regeneration - Nemesis can heal rapidly; gunshot wounds will close almost immediately. More serious injuries will take longer to heal.
- Mutation - If its limiter coat is lost, Nemesis will begin to mutate. Initially, this will result in the growth of additional tentacles or bony spikes across the back, but further injury will result in more extreme transformations. By the time it confronted Jill and Carlos in the Dead Factory, the Nemesis had transformed into a quadraped creature with just a gaping, spiky maw rather than a head. It also developed large, acid-filled pustules on its back and could release this substance from its tentacles. By the time it mutates to this point, the Nemesis is completely uncontrollable.