Background: This systematic review aims to identify out-of-school time (OST) interventions (eg, programming, policies) that increased opportunities for physical activity (PA) and healthy eating and/or improved youth PA and dietary behaviors. Methods: We searched for articles within systematic reviews that met our criteria (2010-2018) and for individual articles (2010-2020). Reviewer pairs screened articles, double-extracted data, assessed risk of bias (RoB), and achieved consensus. We included 71 articles (55 studies, 60 intervention arms). Results: Health (n = 3) and nutrition education (n = 7) interventions showed promising results, but most used weak designs and had high RoB. PA-focused interventions (n = 23) were largely consistent in improving fitness and moderate to vigorous PA during programming. Programmatic interventions that improved both PA and nutrition outcomes engaged family or community members (n = 4/13). Most organizational policy interventions improved the nutrition environment and student PA during OST. Conclusions: Organization-level policy and programmatic interventions can improve environmental supports and youth behaviors during OST programming, complementing school-day efforts to address student PA and dietary intake. To maximize their potential impact, OST programs need to be accessible to families. Administrators can consider actions to reduce participation barriers.