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As Season 4 begins, Doctor Octopus allies himself with Arnim Zola and HYDRA and begins to form a new iteration of the Sinister Six starting with Kraven the Hunter. When Doctor Octopus attempts to turn Norman Osborn back into Green Goblin, he finds that Osborn injected himself with an anti-Goblin serum to prevent further transformations. Doctor Octopus uses the Siege Perilous to summon the Green Goblin's demonic winged counterpart from Miles Morales's universe and after a brief battle recruits him instead. Then it is revealed that Rhino has become a spy for Doctor Octopus while operating as a student at the S.H.I.E.L.D. Academy in exchange for finding a cure for his condition (since he gained his powers by drinking one of Doc Ock's animal serums). Now titled Ultimate Spider-Man vs the Sinister 6, the show will see Spider-Man fighting evil with the help of S.H.I.E.L.D. and his own team consisting of Agent Venom, Iron Spider, Miles Morales (going by the name Kid Arachnid), and the newly introduced Kaine/Scarlet Spider, as well as S.H.I.E.L.D. operatives Leo Fitz and Jemma Simmons.
Peter Parker must find a way to stop Doctor Octopus and the Superior Sinister Six from destroying all of the heroes in New York and taking over the world.
Doctor Octopus threatens to harm Aunt May if Spidey ever puts on his mask again; Spider-Man must track down Doc Ock before he has a chance to put his plan into action.
On Christmas Eve while house-sitting, Spidey must team up with the half-crazed Moon Knight to defend the house against the new Mysterio.
Spider-Man puts the Triskelion on lockdown when a mysterious villain begins to take out the heroes one at a time.
Spider-Man and Scarlet Spider have to infiltrate the sunken Hydra Island so Scarlet can destroy the lab that created him.
Spider-Man must team with the former traitor, Scarlet Spider, to stop Doc Ock from reawakening a secret program designed to create evil duplicates of Spider-Man.
It's Halloween, and Spider-Man is in for a treat. All the trick-or-treating kids have been turned into the real life versions of their costumes, and it's up to Spider-Man, Ant-Man and Doctor Strange to turn the city back to normal.
Spider-Man returns to Miles Morales' universe after collecting all the shards of the Siege Perilous and finally confronts Wolf Spider.
Spider-Man and Kid Arachnid attempt to prevent Mr. Negative from using the Siege Perilous to drain all the life and color out of the Noir Universe.
Spider-Man and Miles track the missing pieces of the Siege Perilous to a tropical pirate dimension, where they encounter Web Beard, the Spider-Pirate.
Spider-Man and Kid Arachnid travel to alternate dimensions in order to gather the shards from the broken Siege Perilous.
Spider-Man and his fellow heroes have to defeat Morbius and his plan to use the Carnage Queen as a weapon.
Spider-Man, Captain America and S.H.I.E.L.D. Academy must band together to save New York.
Spider-Man and Agent Venom uncover Hydra and Morbius' plan to create a new, improved Venom Bomb.
When a battered Nova asks for help finding Nick Fury, Spider-Man tracks him to the dangerous ruins of an ancient city.
When Doc Ock learns that the key to a device that will retrieve Hydra Island is at Aunt May's house, Spider-Man must fight to protect his family.
Spider-Man faces the culmination of all Doc Ock's evil machinations when the new Sinister Six assaults the Web Warriors and S.H.I.E.L.D. Academy at the Triskelion.
After receiving a mysterious signal from an unknown base, Spider-Man traces it to an abandoned building in the hopes of finding Nick Fury.
Doc Ock and his new assistant, Morbius, create Anti-Venom in order to destroy one of the Web Warriors.
Spider-Man and Iron Spider discover Doc Ock has taken control of Sandman.
Spider-Man and Scarlet Spider must overcome Kraven in order to rescue their kidnapped teammate, Agent Venom.
After Spider-Man and the Web Warriors are told by Vulture that there is a spy among the other heroes, he and the Web Warriors work to find out who it is while Nova and Nick Fury are away on a secret mission. They test out the new training area that was designed by Leo Fitz and Jemma Simmons, only to discover that the robots were sabotaged. Dr. Connors once again becomes Lizard and now sports a contagious bite that turns others into lizards. When everyone ends up infected, it's up to Spider-Man to stop the Lizard and cure everyone before the infection spreads out of the Triskelion. In the end, Rhino is revealed to be the spy as he and Doctor Octopus escape with Agent Venom as their prisoner.
With the Siege Perilous destroyed in the aftermath of the fight with the Ultimate Green Goblin, Miles Morales is forced to stay in Spider-Man's reality until S.H.I.E.L.D. can find a way to get him and his world's Goblin back to their home. Now dubbed Kid Arachnid, he and Spider-Man must help Norman Osborn when he is targeted by Doctor Octopus and Vulture.
When Doc Ock and Baron Mordo use the Siege Perilous to pull in the Goblin from another universe, Spider-Man enlists the help of Miles Morales and Doctor Strange to try to keep reality from collapsing.
After being saved by Scarlet Spider following Arnim Zola's takeover of the S.H.I.E.L.D. Tri-Carrier, Spider-Man must work with him to liberate Manhattan and his fellow students from HYDRA's clutches. Even when they save Agent Venom and Iron Spider, they must also undo transformations of the HYDRA Goblins, avoid Doctor Octopus and Kraven the Hunter, and defeat Arnim Zola.
Peter Parker learns Doctor Octopus has teamed up with Arnim Zola and Hydra to attack the Tri-Carrier, leaving S.H.I.E.L.D. caught off-guard and Spider-Man left to single-handedly stop the assault. He assembles a new team, including an apprehensive Scarlet Spider, in order to stop the villains from taking over New York.
As Season 4 begins, Doctor Octopus allies himself with Arnim Zola and HYDRA and begins to form a new iteration of the Sinister Six starting with Kraven the Hunter. When Doctor Octopus attempts to turn Norman Osborn back into Green Goblin, he finds that Osborn injected himself with an anti-Goblin serum to prevent further transformations. Doctor Octopus uses the Siege Perilous to summon the Green Goblin's demonic winged counterpart from Miles Morales's universe and after a brief battle recruits him instead. Then it is revealed that Rhino has become a spy for Doctor Octopus while operating as a student at the S.H.I.E.L.D. Academy in exchange for finding a cure for his condition (since he gained his powers by drinking one of Doc Ock's animal serums). Now titled Ultimate Spider-Man vs the Sinister 6, the show will see Spider-Man fighting evil with the help of S.H.I.E.L.D. and his own team consisting of Agent Venom, Iron Spider, Miles Morales (going by the name Kid Arachnid), and the newly introduced Kaine/Scarlet Spider, as well as S.H.I.E.L.D. operatives Leo Fitz and Jemma Simmons.
Peter Parker has been Spider-Man for a year. He has saved lives and fought supervillains, but is still in the process of learning how to be a superhero. Nick Fury of S.H.I.E.L.D. offers Peter the chance to train to be a real superhero and become "The Ultimate Spider-Man". However, Peter will first have to learn how to work with a team of four fellow teenage superheroes who are also under the training program of S.H.I.E.L.D.. The teen heroes that Spider-Man will be teaming up with are Nova, White Tiger, Iron Fist, and Power Man.