Hantaviruses are globally distributed zoonotic negative-sense single-stranded RNA viruses responsible for hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), also termed hantavirus cardiopulmonary syndrome. Human infection occurs predominantly through inhalation of aerosolized rodent saliva, urine, or feces contaminated with hantaviruses. Compared with the general population, infected individuals exhibit markedly increased risks of endothelial dysfunction, capillary leakage, thrombocytopenia, acute kidney injury, pulmonary edema, cardiogenic shock, cytokine storm, and multisystem inflammatory failure. Although rodent-to-human transmission remains the principal route of infection, Andes virus has demonstrated limited human-to-human transmission. The pathogenesis of hantavirus infection involves endothelial invasion, dysregulated innate and adaptive immune activation, cytokine-mediated vascular injury, complement activation, coagulation abnormalities, and inflammatory endothelial dysfunction. Viral glycoproteins facilitate cellular attachment through β3 integrins, protocadherin-1, and other endothelial receptors, promoting viral entry and systemic dissemination. Recent evidence additionally suggests that gut microbial dysbiosis, intestinal barrier dysfunction, and microbial translocation may amplify systemic inflammation through the gut–lung and gut–immune axes. Clinically, hantavirus infection presents with highly variable manifestations ranging from mild febrile illness to fulminant respiratory failure, hemorrhage, renal dysfunction, and circulatory collapse. Diagnosis relies upon epidemiological exposure history, serological testing, reverse transcription polymerase chain reaction, and supportive laboratory findings. Current management remains primarily supportive and includes hemodynamic stabilization, oxygen therapy, mechanical ventilation, renal replacement therapy, and extracorporeal membrane oxygenation in severe disease. This descriptive review summarizes the contemporary understanding of hantavirus microbiology, epidemiology, pathogenesis, gut microbial interactions, clinical manifestations, diagnosis, differential diagnosis, treatment strategies, prognosis, limitations, and future directions while emphasizing the significant inflammatory and vascular burden associated with hantavirus disease compared with the general population.