This study assessed the environmental footprint of emerging micropollutants in Cambodia and France. The aim was to develop and apply an analytical method to detect micropollutants in diverse water sources and climatic regions. Consequently, an analytical method, using online solid-phase extraction coupled with an ultra-performance liquid chromatography-tandem mass spectrometer (online-SPE-UPLC-MS/MS), was successfully developed and validated. This method permits the accurate and rapid multi-residual determination of 15 emerging micropollutants in water at low detection and quantification limits, around 10 ng.L−1 and 30 ng.L−1, respectively, within a total analytical run of seven minutes, including the equilibrium step. The findings revealed that no water body was free of micropollutants in any case of its sources (effluent wastewater, surface water, and even tap water). In surface water, 13 and 11 of the 15 target micropollutants were detected at least once in the Couesnon River (France) and Upper Mekong River (Cambodia), respectively. The concentration of micropollutant detected in Couesnon River ranged from 6–975.5 ng.L−1, with tramadol having the highest concentration. In the Upper Mekong River, the concentration detected ranged from 5–240 ng.L−1, with ketoprofen having the highest concentration. Caffeine was found in the highest concentration in the treated effluent of a Cambodian wastewater treatment plant (WWTP).