Rs9939609 marker in FTO Alpha-Ketoglutarate-Dependent Dioxygenase (FTO) gene, rs7895307 in Transcription Factor 7-Like 2 (TCF7L2) gene, and rs75493593 in Solute Carrier Family 16 Member 11 (SLC16A11) gene have been associated with anthropometric, metabolic, and clinical variables, but have not been concurrently studied in Mexican children and adolescents with adiposity or mental disorders. In this cross-sectional association study, we genotyped these markers by means of TaqMan real-time polymerase chain reaction in two at-risk pediatric cohorts recruited in Mexico City. Group 1 (n = 175) comprised children and adolescents with overweight/obesity. Group 2 (n = 296) consisted of non-medicated adolescents meeting the Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria for Attention Deficit/Hyperactivity Disorder or a mood disorder. Anthropometric measurements (body mass index —BMI—, waist circumference, body fat percentage), metabolic indices (fasting glucose, lipid profile, Homeostatic Model Assessment for Insulin Resistance), and psychiatric diagnoses were evaluated. In Group 1, the FTO A allele (genotypes AA/AT) was significantly associated with severe obesity according to BMI Z scores (p = 0.004, O.R. 3.33, 95% CI [1.42–7.77]), and it was a predictor of waist circumference (B = 6.16, 95% CI [1.78–10.55], p = 0.006) and muscle percentage (B = 4.21%, 95% CI [0.91–7.51%], p = 0.013) using linear regression models adjusted for age and sex. In Group 2, TCF7L2 AA genotype was associated with increased odds of depression (B = 0.83, p = 0.003, OR = 2.29, 95% CI [1.32–3.96]). While SLC16A11 G allele showed a possible association with insulin resistance or glucose levels, confirmation is needed. These exploratory results highlight the need for larger, well characterized cohort studies to confirm the associations.