Background <p>Problematic social media use (PSMU) has become a critical public health issue, with adolescents being one of the most engaged demographic. However, little is known about how distinct social support systems shape the associations between PSMU, mental health, and substance use.</p> Objective <p>The first objective was to compare how support systems (peer, classmate, teacher, family, and self) shape the associations between PSMU, mental health, and substance use. The second objective was to explore which support systems are most prominent among boys and girls.</p> Methodology <p>A representative sample of 5,487 Czech adolescents (50.88% boys, mean age = 15.48, SD = 0.53) was used for the analysis from the 2022 Health Behaviour in School-aged Children study. A network analysis based on undirected Mixed Graphical Models was used to examine the associations. Separate networks for each support system, stratified by gender, were estimated and compared.</p> Results <p>Teacher and classmate support altered the associations in boys, while peer support was more prominent for girls. Family support altered both networks, though its function varied between genders. Self-support functioned as a bridge symptom in both genders, connecting PSMU with mental health and well-being, particularly in girls. In boys, classmate and family support made the association between PSMU and heated tobacco use as well as irritability absent, whereas in girls, peer and family support shaped the links between PSMU and well-being.</p> Conclusion <p>The findings highlight the gender-specific nature of support systems and underscore the need for more nuanced approaches when facilitating external and internal support in adolescents.</p>