Spider-Man, Power Man, Nick Fury, and Phil Coulson lead a S.H.I.E.L.D. mission against the Zodiac. The mission is to obtain a large golden key called the Zodiac Key that is being used by the Zodiac in their volcano-located base to create a formula that, when consumed, gives the user immense superpowers.
Fury and Coulson use a large amount of explosives to open a passageway so that Spider-Man and Power Man can get through. The two heroes go into the base's surveillance room to locate the key. Spider-Man finds it, and asks Power Man if he found anything else. To both of their shocks, Power Man discovers his own parents, Walter and Amanda, working on the formula.
Luke recalls to Spider-Man a time when, before he joined S.H.I.E.L.D., his parents had taken him on vacation in a private jet, but it was really a mission for S.H.I.E.L.D. to escort the same formula Zodiac is making in the present. Scorpio attacked the plane and confronted Walter, while Amanda gave a confused Luke the formula and got him to escape the plane. Luke received the powers that made him Power Man just before hitting the water below, allowing him to survive the fall, but shortly afterwards the plane mysteriously exploded in midair, causing everyone to think that Luke's parents were dead. Luke was soon rescued by S.H.I.E.L.D. and then joined their program.
Worrying about his parents' welfare, Power Man scampers off to look for them. Spider-Man goes after him to try and change his mind, but he refuses, so Spider-Man goes for the key alone. He quickly finds it, but as he takes it out of a slot the ground around him starts to crumble. It is quickly revealed that the key is not powering the formula's creation process, but the entire base.
Spider-Man goes back over the Power Man, who has found the room where his parents are. Going inside, Power Man does not reveal that he is their son to them, believing that now wasn't the proper time to tell them. As such, his parents haplessly attack them when they try to get them out of the base, as does Scorpio. Scorpio goes for the key, which Spider-Man hung around his neck with his webbing. As Scorpio fights Spider-Man, it is revealed that the key can fire energy beams from its tip. Meanwhile, Power Man continues to try to get his parents to safety, but they refuse. Scorpio then throws Power Man into a deep hole that is full of magma at the bottom. Spider-Man then reveals the truth about Luke to his parents, who start attacking Scorpio. Spider-Man gets Power Man out of the pit using the key's energy to get Power Man out of the pit, and Power Man attacks Scorpio alone. Scorpio them takes some of the complete formula, causing extremely immense (and growing) Power Man-related powers. Spider-Man then tries to get the Cage parents to safety, but they reveal that the formula causes the user to explode after a few seconds, and that Power Man needs to come to. Spider-Man and Power Man get Scorpio to fall into the magma pit, where he explodes. Power Man then reunites with his parents.
Outside, Max Fury is found unharmed but depowered, and Nick Fury reunites with Luke's parents. Peter asks Luke if he is doing okay, and Luke says he's never felt better.
Awesome Android accidentally frees Sandman who ends up stopping Awesome Android and putting out the fire Awesome Android caused. Sandman stated to Spider-Man that he just wanted to help. Nick Fury mentioned that he S.H.I.E.L.D. has been working to rehabilitate Sandman and hoping to make him a hero. Spider-Man has Nick Fury let him train him to be a hero. Sandman is outfitted into a special containment suit that limits his power by Water Cage and Amanda Cage. While S.H.I.E.L.D. Agents observe Spider-Man's program, Spider-Man takes Sandman to battle Swarm where Sandman's containment suit is targeted by Swarm. Spider-Man is forced to get the containment suit off of Sandman who then pummels Swarm into submission. Sandman is brought into control and apologizes for his actions. With advise from Iron Fist, Spider-Man trains Sandman (whose containment suit has been replaced) into being a man first and a Sandman second. When Batroc the Leaper is in the middle of a robbery, Sandman springs into action where he attacks Batroc the Leaper. When Batroc the Leaper throws a garbage at Sandman, he ends up attack Batroc the Leaper as J. Jonah Jameson makes a bad comment towards Sandman. Sandman loses control of his emotions and breaks out of his suit where he attacks Spider-Man with a sandstorm attack. Nick Fury sends the rest of Spider-Man's team to help Spider-Man stop Sandman. Spider-Man denies Nova's plan to turn Sandman into glass again as Spider-Man has a different plan. Spider-Man then tries to reason with Sandman until Nova arrives and Spider-Man throws Awesome Android into Sandman's mouth where he absorbs Sandman. When S.H.I.E.L.D. Agents arrive with a new containment suit, Sandman is shot into the containment suit and taken into S.H.I.E.L.D. custody.
Following the fight with the Sinister Six, Norman Osborn has been transformed into Green Goblin again and has captured Spider-Man's team (who have been previously defeated by the Sinister Six). As Spider-Man finds out later, Green Goblin has transformed his friends and plans to use the old Heli-Carrier (now dubbed the "Hell-Carrier") to gas New York City and turn them all into goblins. Now Spider-Man fights alone on the Helicarrier against his own team. Forced to find back up, Spider-Man flees into the city, but is pursued by the team. He is rescued by Coulson, who drops him back on the Helicarrier with a serum created by Dr. Connors that can restore goblins to human form. Dividing and conquering the team with the serum, Spider-Man changes them back by going over each of their origins as well. They confront the Goblin, who presses a button that launches gas-filled missiles, but they are destroyed by S.H.I.E.L.D. The Goblin sets off explosions that put the team in jeopardy. While the boys of the team are rescued, Spider-Man and White Tiger stay behind to fetch Osborn. Osborn sends them flying, but Nova gets White Tiger and later Spider-Man, but not before Osborn falls into the water. He is then placed in custody, now forever a goblin.
Back on the Tri-Carrier, the team congratulates Spider-Man for saving them. Because of his superb bravery, he is offered a place on the Avengers. The season ends with this cliffhanger.