Environmental exposure risk to different xenobiotics, which can potentially alter the function of the endocrine system, remains a great health and safety concern for aquatic species and humans. Steroid hormones, pharmaceuticals and personal care products (PPCPs) have been identified as important aquatic contaminants due to their widespread occurrence in surface waters and their endocrine disrupting properties. Heavily populated areas in South Florida not served by municipal wastewater collection present an unexpected high risk of anthropogenic contaminants to nearby coastal systems through surface runoff and groundwater flow. Previous studies in South Florida have been largely concentrated on assessing the relevance of the fate and transport of inorganic nutrients, heavy metals and pesticides with regulatory criteria. Therefore, a significant gap exists in assessing occurrence, distribution and biological significance of the presence of human related organic contaminants in natural surface waters. In this study, we have developed a fast and sensitive online solid-phase extraction followed by liquid chromatography-high resolution mass spectrometry (SPE-LC-HRMS) method using a Q-Exactive system for the determination of the occurrence and distribution of selected wastewater tracers/indicators, recalcitrant PPCPs and steroid hormones in South Florida surface waters. Seasonal and spatial variations of these contaminants were monitored from 2017 to 2019. The presence of total coliforms and E. coli were also evaluated in order to further assess water quality. Correlations between hormones and anthropogenic tracers were explored to better elucidate the sources, pathways and exposure risks to these contaminants. Caffeine, sucralose, Diethyl-m-toluamide (DEET) and carbamazepine were frequently detected in the water samples, which is indicative of extensive wastewater intrusion impacting the surface water. Estrone (E1), 17-β-estradiol (E2), and 17-α-ethynylestradiol (EE2) levels found in surface water raises concern of potential endocrine disruption effects in the aquatic ecosystem. Hazard quotient has been calculated to identify areas with high ecological risks to aquatic organisms.