Hantavirus pulmonary syndrome (HPS) is a severe disease first recognised in the United States in 1993, with a case fatality rate approaching 35–50%. Since the identification of Sin Nombre virus during the Four Corners outbreak, understanding the transmission dynamics and geographic distribution of hantaviruses has become critical for public health planning and prevention. This review synthesises evidence from ecological niche modelling, epidemiological surveillance, and environmental analyses to explain patterns of hantavirus occurrence in North America. The findings indicate that HPS risk is associated with dry climates, rural and peri-urban landscapes, rodent host ecology, and increased social vulnerability, with cases primarily concentrated in the western United States. We examine how environmental conditions, rodent ecology, human–rodent interactions, and socioeconomic factors interact to influence disease risk. This synthesis provides recommendations for reducing exposure in high-risk populations and regions.