ImportanceIn response to widespread concerns about social media’s influence on adolescent mental health, most research has studied adolescents from the general population, overlooking clinical groups.ObjectiveTo synthesize, quantify, and compare evidence on the association between social media use and internalizing symptoms in adolescent clinical and community samples.Data SourcesPeer-reviewed publications from MEDLINE, Web of Science, PsycInfo, and Scopus (initially reviewed in May 2022 and updated in October 2023) and preprints from Europe PubMed Central (February 2023) published in English between 2007 and 2023.Study SelectionTwo blinded reviewers initially identified 14 211 cross-sectional and longitudinal studies quantifying the association between social media use and internalizing symptoms, excluding experimental studies and randomized clinical trials.Data Extraction and SynthesisPRISMA and MOOSE guidelines were followed, pooling data using a random-effects model and robust variance estimation. The quality of evidence was assessed using the Quality of Survey Studies in Psychology Checklist.Main Outcomes and MeasuresArticles were included if they reported at least 1 quantitative measure of social media use (time spent, active vs passive use, activity, content, user perception, and other) and internalizing symptoms (anxiety, depression, or both).ResultsThe 143 studies reviewed included 1 094 890 adolescents and 886 effect sizes, 11% of which examined clinical samples. In these samples, a positive and significant meta-correlation was found between social media use and internalizing symptoms, both for time spent (n = 2893; r, 0.08; 95% CI, 0.01 to 0.15; P = .03; I2, 57.83) and user engagement (n = 859; r, 0.12; 95% CI, 0.09 to 0.15; P = .002; I2, 82.67). These associations mirrored those in community samples.Conclusions and RelevanceThe findings in this study highlight a lack of research on clinical populations, a critical gap considering public concerns about the increase in adolescent mental health symptoms at clinical levels. This paucity of evidence not only restricts the generalizability of existing research but also hinders our ability to evaluate and compare the link between social media use and mental health in clinical vs nonclinical populations.