Background: Berlin is internationally known for its nightlife. In a nation-wide and Europe-wide comparison, the use of legal and illegal substances is comparatively higher in Berlin than in other similar cities. However, few data exist about the drug use in the party scene. Objective: This study aims to assess the sociodemographic characteristics of Berlin’s party scene and its patterns of substance use as well as expectations towards prevention in order to derive appropriate preventive measures. Methods: Using questionnaires, both online (n = 674) and in the field (n = 203), a total of 877 people of the Berlin party scene were interviewed. The questionnaires ascertained the demographic information of the participants and patterns of substance use in the scene. It also collected the demand for consulting services and personal assessments on the usefulness of prospective and existing prevention programs and offers. Results: The study participants were 29 years old (SD 7.5); 43% were female. Alcohol is the most common substance in the party scene, followed by cannabis, MDMA/Ecstasy, amphetamine, cocaine, and ketamine. In this particular cohort, methamphetamine and “legal highs” did not play a major role. The most demanded preventive measure was more education about drugs and the so called drug-checking. Conclusions: Prevention in this area is both needed and requested, and an expansion of the existing programs (e.g., by so far politically controversial drug-checking) should be considered.