Increasing physical inactivity levels in the Middle East and North Africa (MENA) region is a public health concern. We aimed to synthesize barriers and facilitators to physical activity and make appropriate recommendations to address physical inactivity. We conducted an overview of systematic reviews on physical activity barriers and facilitators in 20 MENA countries by systematically searching MEDLINE/PubMed and Google Scholar for systematic reviews published between 2008 and 2020. Our overview included four systematic reviews and 119 primary studies with data from 17 MENA countries. Lack of suitable sports facilities, time, social support and motivation, gender and cultural norms, harsh weather, and hot climate were the most commonly reported barriers to physical activity. Socio-demographic factors negatively associated with physical activity participation include advanced age, being female, less educated, and being married. Motivation to gain health benefits, losing/maintaining weight, being male, dietary habits, recreation, and increased Body Mass Index are positively associated with increased levels of physical activity. Interventions promoting physical activity in MENA should target schoolchildren, women and girls, working parents, and the elderly. Country-specific sociocultural and environmental factors influencing physical activity should be considered in the design of interventions. Current and future policies and national interventions must be consistently evaluated for effectiveness and desired outcomes.