Pharmaceutical residues in surface waters represent a growing environmental concern due to their persistence and ecological impacts. This review summarizes recent European and Balkan studies (2013–2024) on the occurrence, distribution, and environmental risks of widely used non-steroidal anti-inflammatory drugs (NSAIDs), metformin, and key metabolites such as 2-hydroxyibuprofen. Data from 308 samples across 70 monitoring sites reveal widespread contamination, with diclofenac and ibuprofen detected at up to several μg/L, particularly near wastewater treatment plant discharges. Metabolites frequently exceeded parent compound concentrations, highlighting monitoring gaps. Risk assessments indicate potential harm to aquatic ecosystems, with hazard quotients often surpassing safety thresholds, especially under low-flow conditions. This review underscores the need for enhanced monitoring frameworks incorporating pharmaceutical metabolites. Strengthening regulatory compliance, particularly in Balkan countries with insufficient treatment infrastructure, is critical for safeguarding surface water quality. Integrating pharmaceutical contamination data into ecological engineering practices offers pathways for effective pollution mitigation and sustainable water resource management.