During a conflict, there is significant disability related to common mental health problems, including depression, anxiety, and substance misuse. A self-administered questionnaire was used in a cross-sectional study that was conducted in 2016 to investigate the prevalence of and risk factors associated with psychoactive substance (PS) use among 950 teenagers in different conflict zones in the West Bank. Refugee teenagers were particularly vulnerable to PS use for different reasons, including the availability of substances, the ease of accessing them, the need to cope with problems, and social/peer pressure. The combined use of PS warrants attention due to the potential for physical and mental health risks. PS use was associated with greater odds of violence, which was more evident among refugee users than among other users. Given the multiple factors that influence adolescent PS use in refugee camps specifically, early detection and prevention strategies are essential for this target population. Keywords: drug misuse, Palestinian refugees; conflict zone; mental health problems; psychoactive substances