The goal of this systematic review is to synthesize the published meta-analyses assessing the role of nutritional, behavioral and physical activity factors/interventions on the prevention or treatment of pediatric and adolescent obesity. An online search was conducted in PubMed (end-of-search: September 30, 2015); English-language meta-analyses pooling observational and/or interventional studies examining weight-related indices on children and adolescents were included. Sixty-six meta-analyses corresponding to more than 900,000 children and adolescents were retrieved. The majority of meta-analyses included interventional studies most of which referred to mixed or combined interventions, including components such as diet, physical activity and sedentary behavior reduction. Discrepancies between meta-analyses on observational and interventional studies were noted. Combined interventions including physical activity and nutritional modifications seemed to represent the most effective means for tackling childhood obesity. Synthesis of interventional or observational evidence may yield discrepant results. The combination of enhanced physical activity and improved nutrition emerged as a promising intervention in the fight against childhood/adolescent obesity. However, further research is needed about the most effective multidimensional prevention strategy.