Le père de l'auteur, Vladek, juif polonais, rescapé d'Auschwitz, raconte sa vie de 1930 à 1944, date de sa déportation. Ce récit est rapporté sous la forme d'une bande dessinée dont les personnages ont une tête d'animal : les juifs sont des souris, les nazis des chats, les Polonais des porcs et les Américains des chiens.
Le monde tel que nous le connaissions n'existe plus. La Terre, ravagée par une mystérieuse épidémie, est devenue un cimetière à ciel ouvert. Pire, les morts ne meurent plus et errent à la recherche des derniers humains pour s'en repaître. Parmi les survivants, Rick, policier, se réveille d'un long coma pour découvrir ce que son monde est devenu. Le choc passé, il doit désormais apprendre à survivre...
Spider-Man se voit offrir un nouveau costume de la part de son nouveau meilleur ami... Tony Stark ! Et les liens tissés aujourd'hui vont déterminer le choix de Spidey durant le conflit à venir. Les Quatre Fantastiques, quant à eux, enquêtent sur un mystérieux objet tombé du ciel tandis que l'équipe la plus secrète de l'univers Marvel, les Illuminati, se reforme. Enfin, les New Warriors deviennent les stars d'une émission de téléréalité et parcourent les routes des États-Unis à la recherche de nouveaux exploits.
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