Dévasté par la disparition d'Iron Man, son mentor, Peter Parker a pour projet de laisser son costume de super-héros derrière lui pendant quelques semaines afin de partir en vacances en Europe avec ses camarades lycéens, mais cette escapade est rapidement compromise quand il accepte à contrecœur d'aider Nick Fury à découvrir le mystère de plusieurs attaques de créatures, qui ravagent le continent.
Spider-Man : New Generation présente Miles Morales, un adolescent vivant à Brooklyn, et révèle les possibilités illimitées du Spider-Verse, un univers où plus d’un peut porter le masque…
En Chine, un groupe de scientifiques découvre la momie d'un empereur chinois datant de 200 avant J.C. dans une tombe se trouvant dans un labyrinthe d'une caverne truffée de pièges mortels. Mais leur découverte libère accidentellement une horde d'araignées mangeuses d'hommes. Pour atteindre la sortie, ils vont devoir lutter contre ses arachnides sanguinaires.
Père adoptif de Gamora et Nébula, Thanos a commencé à recueillir les six Pierres d'Infinité : la Pierre du Pouvoir, la Pierre de l'Espace, la Pierre de Réalité, la Pierre de l'Âme, la Pierre du Temps et la Pierre de l'Esprit. Son objectif est de réunir ces six gemmes sur un gantelet doré, forgé par le nain Eitri sur Nidavellir, afin d'utiliser leur immense puissance pour détruire la moitié de la population de l'Univers et rétablir ainsi un certain équilibre. Dans sa quête le menant sur diverses planètes, la Terre, Knowhere et Vormir, Thanos est aidé par ses enfants adoptifs : Ebony Maw , Cull Obsidian , Corvus Glaive et Proxima Midnight . Face à cette nouvelle menace qui concerne l'Univers entier, le groupe de super-héros des Avengers, divisé depuis 2 ans, doit se reformer, et s'associer au Docteur Strange, aux Gardiens de la Galaxie et au peuple du Wakanda.
À la suite de sa participation à l'affrontement entre Iron Man et Captain America, Peter Parker, un jeune lycéen fréquentant le lycée de Midtown, continue à se servir de ses pouvoirs sous le masque de Spider-Man pour lutter contre la criminalité qui ronge la ville de New York, tout en essayant de trouver un équilibre entre sa vie de lycéen, son amour secret pour Liz, son ami Ned Leeds, et sa carrière de super-héros masqué. Mais avec la venue d'un nouveau super-vilain nommé le Vautour équipé d'un exosquelette créé à partir de technologie Chitauri (récupérée après la bataille de New York), Peter devra faire ses preuves en affrontant ce dernier pour prouver à Tony Stark qu'il peut être un atout pour l'équipe des Avengers.
Le Soldat de l'Hiver (alias Bucky Barnes) a autrefois été reconditionné dans une base militaire soviétique sibérienne et hypnotisé à l'aide de certains mots. Quiconque prononce ces mots en russe plonge le Soldat de l'Hiver en transe et peut lui donner n'importe quel ordre sans qu'il puisse désobéir. C'est ainsi qu'en 1991, le Soldat de l'Hiver a provoqué l'arrêt brutal d'une voiture pour s'emparer dans son coffre d'une valise avec un étrange contenu.
OsCorp scientist Richard Parker records a video message to explain his disappearance. Later, he and his wife, Mary, are aboard a private jet hijacked by a man sent to assassinate Richard. The plane crashes, killing both Richard and Mary, after he uploads the video.
Debris from a destroyed Russian space station (where experiments were taking place on huge mutant spiders) fell toward Earth, crashing inside the tunnel of a New York City subway station. The film cuts to the subway station, where Jason, a New York Transit subway supervisor, works. When the debris from the space station crashes into the tunnel, an alarm goes off and the authorities, afraid of a possible disease outbreak, begin evacuating passengers from the station. Jason's coworker Jimmy descends into the subway tunnel to investigate the area, telling Jason that he believes the debris is the remains of the Russian spacecraft. Jimmy feels something bit his leg, and suddenly starts to stumble, falling on the third rail, electrocuting himself. Jason's ex-wife Rachel, who is a coroner with the New York City Dept of Health, discovers a cluster of large, strange-looking "insect eggs" inside Jimmy's body. She saves the eggs in a canister for further study.
Alex Mathis (Greg Grunberg) is a cash-strapped but good-natured exterminator working in Los Angeles. While helping an elderly woman with a rodent problem, he is bitten by a poisonous spider and is treated at a hospital. Meanwhile, a mortician is bitten by a rodent-sized spider that crawls out of a dead body which just arrived at the hospital. Learning of this, Alex offers to take care of the spider in exchange for clearing his hospital bill. José Ramos (Lombardo Boyar), a hospital security guard, offers to help Alex. Going to the morgue, Alex deduces the spider escaped into an air vent. He enters the vent and communicates with José via walkie-talkie. Meanwhile, a military task force led by Major Braxton Tanner (Ray Wise) and Lieutenant Karly Brant (Clare Kramer) show up at the hospital to examine the dead body the spider burst out of.
A young Peter Parker discovers his father Richard Parker's study has been burgled. Gathering up hidden documents, Peter's parents take him to the home of his Aunt May and Uncle Ben, then mysteriously depart.
J. Jonah Jameson is attempting to run the Daily Bugle, which is harassing the "menace" known as Spider-Man, while his employees Betty Brant and Robbie Robertson have intimate relations in a back room. Across town, a power line accident results in an electric company worker being granted the power to generate and control electricity. The worker decides to become a supervillain, and so dons a costume and rechristens himself Electro. Electro hires a prostitute, and electrocutes her after they have sex. The Kingpin of Crime, Wilson Fisk, then approaches Electro, and hires him as part of an elaborate scheme.
Creatures that for years have been rumoured to torment armed forces in the Middle East are inadvertently introduced to the southwestern deserts of the United States. The camel spiders now freely hunt for prey, unafraid of any predator - including man. No place is safe no one is beyond their paralyzing sting. In the end, a small band of hardy fighters are forced to make one last stand against the creatures.
Peter Parker plans to propose to Mary Jane Watson, who has just made her Broadway musical debut. A meteorite crashes near the two in Central Park, and an extraterrestrial symbiote attaches itself to Peter's moped. While fleeing police, escaped prisoner Flint Marko falls into a particle accelerator that fuses his DNA with surrounding sand, allowing him to shapeshift at will as the Sandman. Peter's best friend, Harry Osborn, who blames him for his father's death, attacks Peter using weapons based on his father's Green Goblin technology. Harry injures his head and suffers partial amnesia, forgetting that Peter is Spider-Man and his desire for revenge. During a festival honouring Spider-Man, Marko robs an armored car. NYPD Captain George Stacy tells Peter and Aunt May that Marko was Uncle Ben's killer, and Dennis Carradine was only an accomplice. While a vengeful Peter sleeps, the symbiote bonds with him. Peter wakes up hanging from a skyscraper. His costume becomes black and his powers increase, but the symbiote brings out Peter's dark side. Wearing the new suit, Spider-Man locates Marko and battles him in a subway tunnel, reducing him to mud using water.
Agnes White is a waitress at a gay bar living in a run-down motel in rural Oklahoma. Unable to move on from the disappearance of her son some years previously, she engages in drug and alcohol binges with her lesbian friend, R.C. Lately, she has been plagued by silent telephone calls that she believes are being made by her abusive ex-husband, Jerry Goss, who has recently been released from prison.