Drug abuse imposes substantial societal burdens, health risks, and is linked to increased criminal activity. Monitoring new psychoactive substances (NPSs) and other controlled substances in wastewater using high-resolution mass spectrometry (HRMS) provides real-time insights into patterns of substance abuse. This approach can also identify substances that may not have been seized but are already circulating in the market. In this study, HRMS-based suspect screening was employed to comprehensively identify NPSs and controlled substances in wastewater samples collected from 12 wastewater treatment plants (WWTPs) in Taiwan. Two liters of influent wastewater were collected from each WWTP, and controlled substances were subsequently extracted via solid-phase extraction. The extracts were analyzed by liquid chromatography-HRMS (LC-HRMS) and compared against a suspect list of approximately 700 controlled substances. A total of 336 and 231 suspect features were detected in positive and negative ion modes, respectively, and matched with the suspect list. Forty-four NPSs and controlled substances were further structurally annotated using analytical standards and spectral library matching. Additionally, spatial analysis of drug abundance patterns revealed significant regional variability in drug use across Taiwan.