Nowadays, the contamination caused by emerging pollutants is a global concern due to the lack of scientific evidence to demonstrate the risk or toxicity to humans due to the presence of pharmaceutical residues in the environment. This study aimed to identify and describe the disposal practices of unused and unwanted medications, as well as to analyze and identify the most frequent drugs determined on water bodies adjacent to the biggest urban population in Mexico. A two-phase study with an epidemiological and an ecological assessment was performed. The epidemiological phase was carried out with a descriptive cross-sectional study among citizens from Mexico City and the metropolitan area using an electronic survey applied to 719 subjects aimed to assess practices in which pharmaceutical products are disposed. The ecological phase included a review of scientific reports. The results show that nearly 83.5% of those surveyed use inappropriate practices for disposal medicines, the main ones are through the municipal dump or directly in the drain. The ecological approach was carried out by a systematic literature review of original reports published between 2013 to 2023; information about the class of drugs, active substance, environmental compartments, location, and concentration was extracted and presented. Fifty-one different types of pharmaceutical residues were detected in wastewater in Mexico City in the last decade. The results of this study can contribute to the application of public policies for waste management authorities to mitigate the socio-environmental risks due to the inappropriate disposal of medicines.