This systematic review provides a comprehensive overview of *Hepatozoon* (Eucoccidioida: Hepatozoidae) in wild mammals across the Americas, focusing on epizootiology, diagnostics, genotyping methods, evolutionary relationships, and genetic diversity. The study utilized the PRISMA method to identify 84 relevant studies, with data from 11 out of 35 countries (31.4%). Carnivora and Rodentia were the most characterized orders, while bats, ungulates, and shrews were less affected. Various species of *Hepatozoon*, including *H. americanum*, *H. canis*, *H. didelphidis*, *H. felis*, *H. milleri*, *H. griseisciuri*, and *H. procyanis*, were identified, with many genospecies yet to be formally described. Vectors of *Hepatozoon* include fleas, mites, and ticks, though most vectors remain unknown. Conventional PCR is the primary diagnostic technique, but real-time PCR could improve sensitivity and specificity. Genetic analysis of the V4 region of the 18S rRNA gene revealed two main clades: Clade I associated with small mammals, birds, and herpetozoa, and Clade II associated with Carnivora. The study highlights the potential of *Hepatozoon* as a disease agent in threatened wild mammals and the role of wild canids in spreading infections.This systematic review provides a comprehensive overview of *Hepatozoon* (Eucoccidioida: Hepatozoidae) in wild mammals across the Americas, focusing on epizootiology, diagnostics, genotyping methods, evolutionary relationships, and genetic diversity. The study utilized the PRISMA method to identify 84 relevant studies, with data from 11 out of 35 countries (31.4%). Carnivora and Rodentia were the most characterized orders, while bats, ungulates, and shrews were less affected. Various species of *Hepatozoon*, including *H. americanum*, *H. canis*, *H. didelphidis*, *H. felis*, *H. milleri*, *H. griseisciuri*, and *H. procyanis*, were identified, with many genospecies yet to be formally described. Vectors of *Hepatozoon* include fleas, mites, and ticks, though most vectors remain unknown. Conventional PCR is the primary diagnostic technique, but real-time PCR could improve sensitivity and specificity. Genetic analysis of the V4 region of the 18S rRNA gene revealed two main clades: Clade I associated with small mammals, birds, and herpetozoa, and Clade II associated with Carnivora. The study highlights the potential of *Hepatozoon* as a disease agent in threatened wild mammals and the role of wild canids in spreading infections.