MedNET is the Mediterranean network of the Pompidou Group for co-operation on drugs and addictions. It comprises 18 countries from the northern and southern rims of the Mediterranean. MedSPAD is the Mediterranean School Survey Project on Alcohol and other Drugs. This is the fourth regional report from MedSPAD, and it provides insights into substance use and risk behaviours among adolescents and the socio-economic and policy context in the Mediterranean region. It follows the work presented in the 2019 report “An insight into alcohol, tobacco and other drugs in the Mediterranean region: socio-economic, policy context and patterns of use among adolescents”, which covered 13 countries. For this report, 11 countries – Croatia, Cyprus, Egypt, France, Greece, Italy, Malta, Morocco, Portugal, Spain and Tunisia – provided raw survey data estimating the perceived availability and risk of substances, early onset of substance use, and prevalence of the use of alcohol, tobacco, other substances, gambling, gaming and social media use.