Background: Since overweight and obesity has become epidemic in children and adolescent, the aim of this study was to determine the role of highly-integrated programs in preventing and reducing prevalence of children and adolescent obesity and overweight. Methods: A systematic review of literature and a meta-analysis was conducted. Results: According to PRISMA guidelines, we identified 23 studies describing 14 programs. For 11 out of 14 programs, obese/overweight prevalence changing from baseline were definable and meta-analysis of them showed a significant change of obese/overweight prevalence (-0.03; 95% CI = -0.04 to -0.01; P < 0.0001). Secondary outcomes as dietary (such as vegetable intake, carbonated beverages, fruit juice, drinks, healthful food consumption), physical activity and TV-time-spent was analyzed in many of the studies to define community readiness and behavioral changes. Macro-interventions, based on what was observed in our systematic review have a high potential to reach the entire population. Conclusion: Adoption of coordinated cross-sectoral, multi-component and multi-stakeholder initiatives to oppose obesity remains a challenge, but it is also desirable as one of the possible solutions to this major public health issue.