BACKGROUND AND AIMS: Estimating the retail drug market size is complex due to its clandestine nature, yet useful for intervention and policy planning. Wastewater-based epidemiology (WBE) offers an alternative strategy to estimate population-wide consumption trends by analysing influent wastewater, avoiding self-reporting biases associated with other estimation techniques, e.g., consumption or expenditure-based models. This study evaluates the applicability of WBE for drug market size estimation. METHODS: Using WBE data the drug market situation of amphetamine, cocaine, MDMA, and methamphetamine is estimated in European cities (n=75) through combination with price/purity information (Statistical Bulletin) published by the European Union Drugs Agency. Market sizes were estimated at three levels: (L1) pure drug quantities, (L2) adulterated retail drugs quantities, and (L3) market value. Furthermore, yearly consumption estimates from the commonly applied consecutive seven-day sampling is compared to a randomised stratified sampling approach in Brussels, Belgium. RESULTS: Challenges include the availability and accuracy of price and purity data, which complicates cross-country comparisons and hinders the higher-levels calculations. Due to missing data, the market value (L3) could only be calculated for a limited number of cities, i.e., 39% (amphetamine), 39% (cocaine), 1% (MDMA), and 23% (methamphetamine). Furthermore, statistically significant differences were shown for amphetamine (up to 139% measurement error) and methamphetamine (up to 58% measurement error) between both sampling approaches. CONCLUSIONS: Particularly at city level, WBE can complement traditional market size estimations, but significant uncertainties remain. Future research should expand one-week consecutive sampling to a randomised stratified sampling approach tailored to drug and location.