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Smartphones have become essential components of daily life, and research into the harmful effects of problematic smartphone use (PSU) on mental health is expanding in the Middle East and North Africa (MENA) region. This issue has yet to be synthesized and critically evaluated. To find quantitative observational studies on the relationship between PSU and mental health in the MENA region, we developed a search equation and adapted it for four databases. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines were followed during the selection process. This review included 32 cross-sectional studies and one cohort study. The available language was English. All identified studies published until 8 October 2021, were considered. A modified Newcastle-Ottawa scale was used to assess the quality of the included studies. The studies enrolled 21,487 people and had low-to-moderate methodological quality. The prevalence of PSU ranged from 4.3 to 97.8 percent. The time factor, type of application used on the smartphone, and sociodemographic characteristics were the determinants of PSU. Depression, anxiety, and stress were strongly correlated with PSU. Epidemiological longitudinal studies that respect the quality of evidence are needed in all MENA countries to better plan and implement preventive measures against PSU.