In the year 2099, New York City is a different place than the city it was in the "Heroic Age" of today. Giant corporations run the high-tech city, while the "Public Eye's" cameras monitor for criminal activity. The forgotten and unfortunate live below the towers in the streets of "downtown". Much has changed, but much too has remained "depressingly the same."
Spidey 2099 leaps across town, pursued by the flying police force called the "Public Eye". In the chase, we learn of some of his powers and abilities - incredible agility and reflexes, ability to cling to walls, and sharp claws upon his fingertips. Spidey 2099 evades the Public Eye and returns home to Babylon Towers. Spider-Man 2099 returns to his civilian identity of Miguel O'Hara. He is greeted by his personal hologram, Lyla. Sensitive to the light, Miguel sits in the dark while Lyla plays through several hologram messages: Tyler Stone, his boss - Gabe, his brother - and Dana, his fiance with a noticeable black eye. He ignores his messages, and recounts the events of the past few days into his journal.
Miguel is an employee of Alchemax, project head of the Genetics Program. He is intelligent, confident, and obnoxious, especially to his supervisor, Aaron Delgato. Miguel's research involves alteration in the genetic structure of animals. Part of his "inspiration" for research was the original Spider-Man. Though Miguel prefers to proceed with caution, Aaron and Alchemax CEO Tyler Stone want results immediately. In order to expedite his research Tyler acquired a human test subject, Mr. Sims, a criminal who exchanged his sentence of aging 40 years. Rather than quit in protest, Miguel agrees to do the experiment just to make sure Mr. Sims has a chance of surviving. Miguel tries to increase Mr. Sim's strength in a simple experiment. However, even a simple experiment fails, as Mr. Sims is mutated and dies.
Miguel quits, disgusted by the premature acceleration of his program. Tyler offers Miguel a farewell toast, and promises to deliver high recommendations to any other corporation looking to hire him. Placing Miguel in checkmate, Tyler had drugged Miguel with Rapture, an addictive hallucinogen that binds to the individual on the genetic level. Since only Alchemax legally sells the drug, Miguel would be forced to continue employment at Alchemax or buy the drug through the black market. Once the drug binds to his system, he would need it for the rest of his life.
Returning home, Miguel battles hallucinations. His fiance, Dana, greets him, and notices he looks sick. Miguel strikes her across the face in a delirium. Miguel explains the situation, and Dana suggests going to the black market. Determined not to be a drug addict, Miguel returns to Alchemax and sneaks into his lab. Since he had downloaded his genetic imprint into the computer during his research, he hoped to reset his body to what it was before Tyler drugged him. Aaron discovers Miguel experimenting on himself, and tries to wreck the experiment by overloading the circuitry. The genetic imprint for a spider was accidentally triggered. Miguel emerges from the experiment apparently unharmed. But when Miguel turns around to face Aaron, he's sporting two large fangs and claws!