The use of illicit drugs causes unquestionable societal and economic damage. To implement actions aimed at combating drug abuse, it is necessary to assess illicit drug consumption patterns. The purpose of this paper was to develop, optimize, validate and apply a procedure for determining new psychoactive substances (NPSs) and classic drugs of abuse and their main metabolites in wastewater samples by using solid phase extraction (SPE) and high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Moreover, detailed validation of the procedure was conducted. The developed SPE-HPLC-MS/MS procedure (within the sewage-based epidemiology strategy) allowed for the simultaneous, selective, very sensitive, accurate (recoveries ≥ 80.1%) and precise (CV ≤ 8.1%) determination of new and classic psychoactive substances in wastewater samples. This study is characterized by new scientific elements, especially in terms of the freeze-thaw and post-preparative stability of the selected psychoactive substances. This is the first time that NPSs (mephedrone and ketamine), the main metabolites of heroin (6-acetylmorphine, 6-AM) and marijuana (11-nor-9-carboxy-Δ9-tetrahydrocannabinol, THC-COOH) have been detected and monitored in Poland. This study is also the first to corroborate the data available from the EMCDDA and EUROPOL report and indicates that the retail market for cocaine is expanding in Eastern Europe. Drug abuse and illicit drug trafficking is a global phenomenon that causes a broad spectrum of social, health and economic problems 1-4. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) and the United Nations Office On Drugs and Crime (UNODC) reported that drug-related problems are becoming increasingly complex, especially with regard to the extremely dynamic nature of the new psychoactive substances market, stimulants, misused medicines and problematic cannabis use 3-7. Moreover, the verification of the presence of traditional illegal drugs (i.e., amphetamine, methamphetamine, ecstasy, etc.) in sewage samples is still needed because of environmental and forensic issues 8,9. The environmental impact of synthetic drug production has been highlighted in the last EMCDDA and EUROPOL report 7. Waste from drug production discharged into surface waters may harm aquatic life, can potentially contaminate the meat of cattle, which can affect the human food chain, and could further spread hazardous substances into the soil and waterways 7,10. In this context, it is crucial to pay greater attention to developing new methodologies as tools for monitoring illicit drug consumption and its trends and drug trafficking to combat drug abuse and improve quality of life 11-17. Illegal drug use is mostly an unofficial activity. Consequently, traditional survey methods, such as general population interviews and surveys, can be inaccurate and may also produce results based on conjectures 2,8,18,19. Conventional survey methods are not suitable for monitoring fast-changing drug markets over time 20. T...