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L'histoire se déroule en Allemagne, en 1986, à Düsseldorf. Kenzo Tenma, le personnage principal, est un jeune neurochirurgien très talentueux, destiné à une brillante carrière et fiancé à la fille du directeur de l'hôpital, Eva Heinman. Mais un jour il refuse de soigner le maire et préfère soigner un garçon blessé d'une balle dans la tête. Sa sœur jumelle est aussi internée dans l'hôpital car elle est très choquée. Leurs parents (adoptifs) ont été assassinés sauvagement. Le garçon s'en sort, mais le maire meurt, faute de soins. Tenma est alors rétrogradé par le directeur de l'hôpital et Eva le quitte. Peu de temps après, le garçon et sa sœur disparaissent. Neuf ans plus tard alors que Tenma est sur le point de devenir le directeur d'hôpital, il est accusé de meurtre qui ont en fait été commis par Johann, ce garçon de 11 ans qu'il avait sauvé. Dès lors l'inspecteur Rünge, un homme de caractère et de confiance prend en charge l'enquête. Il poursuit Tenma sans relâche tandis que ce dernier poursuit Johann ; car Tenma, qui se demande s'il n'a pas sauvé un "Monstre", sait que les meurtres sont "l'œuvre" de son ancien patient.
Lorsque d'étranges portails sont apparus aux quatre coins du monde, l'humanité a dû trouver une parade pour ne pas finir massacrée entre les griffes des monstres qu'ils ont apportés avec eux. Dans le même temps, certaines personnes ont développé des capacités permettant de chasser. Ces combattants intrépides n'hésitent pas à foncer au coeur des donjons pour combattre les créatures qu'ils abritent.
Dunwich, village en déliquescence aux confins de la Nouvelle-Angleterre, fait l'objet de nombreuses rumeurs. On dit que les cercles de monolithes au sommet de ses collines étaient jadis le théâtre de rites terrifiants... En 1913, la naissance de Wilbur est un mystère de plus sur cette terre maudite. Sa mère est une albinos aux airs de sorcière, et l'identité du père est tenue secrète par le patriarche Whateley, qui assure qu'il s'agit d'un être supérieur, différent de tout ce qu'il connaît... Les voisins le croient fou, néanmoins le faciès animal du jeune garçon semble appuyer ses dires. Sans compter qu'il grandit à une vitesse fulgurante... À dix ans, il se met en quête d'un ouvrage ésotérique, le Necronomicon, dont il s'enquiert auprès de diverses bibliothèques. Le professeur Armitage de l'université Miskatonic, intrigué par cette demande, se rend sur place pour le rencontrer. L'intelligence de Wilbur l'impressionne, mais quand il voit les murs de l'étage se déformer sous l'effet d'une puissance inconnue, il repart la peur au ventre ! Quelles monstruosités se cachent chez les Whateley ?
