After his fight with Electro and Vulture, Spider-Man falls asleep from exhaustion on a rooftop, awakening the next morning. He calls Yuriko Watanabe to let her know he is going after Scorpion at the city's reservoir.
Upon arrival, Scorpion gets the drop on Spider-Man, using his stinger tail to inject him with poison. The environment then changes as Spider-Man hallucinates the entire area is a sea of poison. After players get to higher ground, they can then perform a spectrograph puzzle to determine what toxin was used. A quick trip to the ESU greenhouse would help in developing an antitoxin, but when players arrive, they are forced into another hallucination environment, this one full of fragmented streets and an Otto Octavius that keeps vanishing as players get close. The end of the sequence results in Spider-Man back in the real world, albeit still hallucinating the sea of poison. With one ingredient in hand, players need to get to one of Harry Osborn's research stations.
For this part, players need to traverse the city while dodging giant scorpion tails that rise up from the poison. Once in the station, another hallucination takes over. Similar to the first, players need to pursue Otto through this sequence, using more advanced webbing techniques. The scene is similar to before, but this time there is more destruction and debris.
More destruction and many more scorpion tails greet players as they return to the real world. With the last of the ingredients he needs, players need to traverse the city and get to Otto's lab to synthesize the antidote. Once there, the final hallucination sequence begins with Doctor Octopus ripping apart the building.
Players fight Scorpion in this round. He can fire poison blasts and leap. Defeating the first is easy, but progressing further involve a fight with multiple Scorpions. They tend to leap around the area for the most part, but players can find themselves fighting more than one at once. Webbing him up is a good strategy, as only a few hits will destroy one of them. Players should be mindful of their tail swipes.
Once successful, players will find themselves back in the lab, with Spider-Man having taken the antidote. He is, however, in his Undies.