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Niko Tatopoulos was a biologist who worked to catalog new species created by the nuclear spill at the Chernobyl spill site. He was picked up via helicopter by the United States military and brought to Panama where he was commissioned to observe a large footprint found there. Nick eventually determined that the creature that left the footprint was some sort of reptile, but was far too large to be a dinosaur. Instead, Nick proposed that it was an entirely new species created by radiation. Eventually, the monster swam up the Atlantic Ocean to the east coast of the United States and came ashore in New York City, causing untold collateral damage. When Nick arrived in New York City, he made it clear that the creature was only acting on instinct, and that the most efficient way to subdue him would be to set a trap. It was concluded that the monster consumed fish, so a large pile of fish was laid in Flatiron Square, and the manholes on the nearby streets were opened. Eventually, the monster emerged from under the street and began to eat the fish. Nick got a chance to get close to the monster and photograph it, but was interrupted when the military opened fire on it. The monster evaded the military and escaped to the ocean. However, Nick was able to secure a blood sample from the monster. The blood sample allowed Nick to discover that although the monster was male, its mutation had given it the unique ability to reproduce asexually. Nick deduced that the monster had not come to New York to simply rampage, but to create a nest and feed his young. Around this time Nick reconnected with his college sweetheart Audrey Timmonds, who he invited to his research station. Realizing that this could be just the story she needed to jump start her career as a reporter, Audrey betrayed Nick and stole some of his research tapes to be used in a news story.
After the story was made public, Nick was kicked off the task force for dealing with the creature. Nick hailed a cab to return to the airport, but discovered that he was being taken against his will to a hidden base. There, he learned that the men who kidnapped him were a group of French secret servicemen, led by Philippe Roaché, who sought to destroy the monster, now dubbed "Godzilla" by the media, because a nuclear test conducted in French Polynesia by their country in 1968 spawned it. Roaché revealed that their plan was to find Godzilla's nest and eliminate it before the eggs could hatch. Tracking Godzilla through the tunnels under Manhattan, Nick and the Frenchmen eventually discovered the monster's nest inside Madison Square Garden. There, they found hundreds of eggs and did not have nearly enough explosives to destroy them. Eventually, the eggs began to hatch, and the hatchlings could smell the scent of fish on Nick and the others. They soon found themselves being chased throughout the arena by countless Baby Godzillas, who killed the rest of Philippe's crew. Inside the Garden, Nick and Philippe encountered Audrey and her cameraman Victor "Animal" Palotti, who were trying to record footage of the nest. Using recording equipment inside the arena, Audrey broadcast a message to all of New York showing the Baby Godzillas running rampant and warning what would happen when they escaped and matured. Colonel Hicks saw the broadcast and ordered an airstrike on Madison Square Garden, which was delivered by three F-18 Hornets just after Nick and the others escaped.
With the Baby Godzillas all dead and Godzilla reportedly killed by submarines in the East River, it seemed that Nick's mission was accomplished and the city was safe. However, he realized this was not the case when the adult Godzilla suddenly burst out from under the street. Seeing its dead offspring along with Nick and the other humans infuriated Godzilla, who began to chase after them. Jacking a taxi cab, Nick and the others fled from Godzilla across the city. After making contact with the military, Nick was told to lure Godzilla to the Brooklyn Bridge. Barely evading Godzilla, the cab reached the bridge, with Godzilla becoming ensnared in the bridge's suspension cables behind it. With Godzilla helpless, three F-18 Hornets flew by and bombarded the monster with missiles relentlessly until it finally collapsed from its injuries. Nick exited the cab and approached the fallen Godzilla, which looked sadly into his eyes before finally dying. New York City burst into celebration, while Nick and Audrey appeared to finally rekindle their romance.
Following Godzilla's death, Nick approached Hicks and warned him that it was possible that one of Godzilla's eggs could have survived the bombing of Madison Square Garden. Nick was sent along with a team of soldiers to investigate the ruins, but he fell into a cavern and was separated from the rest. Nick stumbled upon a surviving egg, which hatched into an infant Godzilla. Rather than attack Nick like its siblings had done, this Godzilla believed Nick to be his father. Nick shooed the monster away, and it burrowed through the ground to safety. Eventually, the rapidly maturing Godzilla arrived at the headquarters of Nick's new scientific organization, H.E.A.T. after being lured there with fish. Nick studied this new Godzilla and concluded that he posed no real danger, being incapable of asexual reproduction and non-hostile to humans. Nick also noticed that Godzilla seemed to display remarkable intelligence and loyalty. Upon discovering that Nick was keeping Godzilla near his lab, Hicks arrived with the military to kill Godzilla. Godzilla was seemingly killed by the military's weapons, but actually escaped to the ocean. Nick then left to go investigate reports of a giant monster attacking Jamaica. There, Nick and his team discovered several Mutant Giant Squids as well as a huge mutated crustacean dubbed Crustaceous Rex. Godzilla, having survived the military's attack, emerged and battled the monster, using his atomic breath to defeat it. Following this, Hicks begrudgingly agreed to allow the new Godzilla to live under Nick's supervision.
Nick and H.E.A.T. then traveled the world answering calls for help from people and places that were being attacked by mutations. He was often forced to defend Godzilla from other parties, such as the United States Military or French Secret Service Agents Philippe Roaché and Monique Dupre. Nick continued to study Godzilla with the help of his colleagues and discovered many things about him. Nick and Godzilla continued to have a close relationship and together were able to save the Earth from many threats.
- Nick Tatopoulos was named after Patrick Tatopoulos, Godzilla's designer for the 1998 film.
- Nick's relationship with the second Godzilla in Godzilla: The Series is reminiscent of Azusa Gojo's relationship with Baby Godzilla in Godzilla vs. MechaGodzilla 2.
- Nick was going to return as the protagonist in the unmade sequel to the 1998 film, as revealed by the film's official screenplay.