Purpose <p>The study aimed to examine whether muscular fitness and adiposity at baseline (age range: 7–16) are associated with clustered cardiometabolic risk at a 3-year follow-up, independent of cardiorespiratory fitness; and to investigate the distinct mediating roles of muscular fitness and adiposity in their potential associations with clustered cardiometabolic risk in a sample of children and adolescents from Southern Brazil.</p> Methods <p>An observational 3-year longitudinal study was conducted including 411 children and adolescents (10.51 ± 2.03&#xa0;years of age at baseline; 56.4% females). Waist circumference was measured in addition to field-based tests of cardiorespiratory fitness, lower limb power, and abdominal muscular endurance. A clustered cardiometabolic risk score was calculated from fasting glucose, systolic blood pressure, total cholesterol/HDL-C ratio, and triglycerides z-scores, which were subsequently summed up and divided by four. Structural equation modeling with bootstrap was applied.</p> Results <p>Both waist circumference and muscular fitness at baseline were significantly associated with the clustered cardiometabolic risk score at follow-up, independently of cardiorespiratory fitness. Specifically, waist circumference showed both direct (<i>β</i> = 0.095; 95% CI 0.025–0.169) and indirect associations through muscular fitness (<i>β</i> =  − 0.042; 95% CI − 0.085 to − 0.013) with cardiometabolic risk. The association between muscular fitness and cardiometabolic risk was explained by waist circumference (<i>β</i> =  − 0.179; 95% CI − 0.511 to − 0.059).</p> Conclusion <p>This study identified a complex longitudinal and synergistic relationship between muscular fitness, adiposity, and cardiometabolic risk. These findings highlight the importance of considering this interplay when designing strategies to improve cardiometabolic health in children and adolescents.</p>