Wastewater-based epidemiology (WBE) is a powerful tool to gather epidemiological insights at the community level, providing objective data on population exposure to harmful substances. A considerable portion of the human exposure to these potentially harmful chemicals occurs unintentionally, unlike substances such as pharmaceuticals, illicit drugs, or alcohol. In this context, this comprehensive review analyzes WBE studies focused on classes of organic chemicals to which humans are unintentionally exposed, namely organophosphorus flame retardants, per- and polyfluoroalkyl substances (PFAS), benzotriazoles and benzothiazoles, phthalates and terephthalates, benzophenones, pesticides, bisphenols, and parabens. The review highlights some advantages of WBE for public health surveillance, e.g., non-invasive analysis, predictive capability, nearly real-time data, population-wide insights, no ethical approval, and unbiased sampling. It also discusses challenges and future research directions in WBE regarding exposure to harmful chemicals from various sources. The review emphasizes the critical role of wastewater sampling, sample preparation, quality control, and instrumental analysis in achieving accurate and reliable results. Furthermore, it examines the selection of human biomarkers for WBE studies and explores strategies to link WBE with human biomonitoring (HBM), which together enhance both the precision and effectiveness of exposure assessments.