Abstract
Wastewater-based epidemiology (WBE) has become a transformative tool for infectious disease surveillance, providing population-level insights that complement and extend traditional case-based reporting. This review examines the expanding role of WBE in identifying and characterizing underreported, novel, and emerging human pathogens. Evidence reveals that wastewater analysis consistently detects enteric, respiratory, and neglected pathogens that are often missed by clinical systems, thereby revealing the hidden burden of infection within communities. Sequencing-based studies have identified numerous novel and divergent human viruses, highlighting the extensive diversity of the human virome. The frequent co-detection of multiple viral taxa also suggests that interactions and co-infections may influence viral evolution, disease manifestation, and transmission. Despite methodological challenges in quantification and biological validation, WBE has proven capable of detecting both known and novel pathogens before they are clinically recognized. Future developments in long-read sequencing, bioinformatics, and global data integration will enhance the precision and scope of wastewater genomics, positioning it as a central element of early-warning and One Health surveillance frameworks. By illuminating the unseen spectrum of infectious agents, WBE bridges environmental and clinical domains, offering a scalable and equitable strategy for global pathogen discovery and public health preparedness.