Using metagenomic next-generation sequencing (mNGS), we identified a variety of vector-borne, zoonotic, and emerging pathogens responsible for undifferentiated fevers in a periurban population in Cambodia. From March 2019 to present, PHD, the National Malaria Center and the Cambodia Communicable Disease Center (CCDC) enrolled more than 2,000 febrile illness cases. We collected sera and prepared sequencing libraries from extracted pathogen RNA for unbiased metagenomic sequencing and subsequent bioinformatic analysis on the global cloud-based platform, CZID. mNGS identified vector-borne pathogens, zoonotic pathogens and outbreak pathogens. Coordinated and ongoing mNGS pathogen surveillance can better identify the breadth of endemic, zoonotic, or emerging pathogens and deployment of rapid public health response.