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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.
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.
Fûtarô, un lycéen brillant mais fauché, décroche un petit boulot de rêve : professeur particulier pour une famille fortunée. Or, le garçon déchante lorsqu'il réalise que ce n'est pas un élève qu'il va devoir gérer, mais des quintuplées aussi belles que cancres à souhait... Entre Ichika la désordonnée, Nino la protectrice, Miku la réservée, Yostuba la joviale et Itsuki la susceptible, Fûtarô va devoir prendre son courage à deux mains pour relever le défi que représentent les sœurs Nakano !
