The detection of pharmaceuticals and personal care products (PPCPs) in environmental matrices raised concerns over their short- and long-term effects on the ecosystem. Wastewater is the primary carrier of PPCPs to the environment in highly urbanized regions. In the Philippines, Manila Bay serves as a drainage basin for most of the streams of surrounding urban cities, hence, a cumulative drainage basin for effluents transported downstream. Water samples from the surface and the bottom layers of Pasig River mouth and Manila Bay were collected for PPCP analysis. Pharmaceuticals and pharmaceutical-related compounds, such as carbamazepine, clarithromycin, diclofenac, anhydroerythromycin, acetylsulfamethoxazole, trimethoprim were detected, as well as possible untreated wastewater tracers like caffeine and acetaminophen. Total concentrations were higher in Pasig River compared to Manila Bay due to the dilution of river water entering a bigger water body. Vertical variations in PPCP concentrations in Pasig River are not significant. In contrast, the top layer of Manila Bay is more contaminated compared to the bottom potentially due to stratification. Differences in PPCP profiles show how variable contaminants depend on external factors. The presence of PPCPs in natural systems highlights the need for more stringent and targeted wastewater management.