Youth violence in Latin America is an important public health problem. However, the evidence from preventive programs within the region to address this problem is limited. Identifying context-specific factors that facilitate or hinder the success of interventions is necessary to guarantee the successful implementation of new preventive strategies. We present a systematic review and synthesis of qualitative studies to identify factors affecting the implementation of programs to prevent youth violence in Latin America. We searched 10 electronic databases and websites of international institutions. The quality of the studies was assessed using the critical appraisal skills program checklist, while the certainty of the findings of the synthesis was assessed using the certainty of the qualitative evidence approach. We included eight papers describing five programs in Argentina, Venezuela, Peru, El Salvador, and Mexico. Most of the factors affecting the implementation of programs were aspects related to features of the programs and social/political constraints. The synthesis suggests that future programs can benefit from having a multidisciplinary and/or multisectoral approach involving different key players. At the same time, potential strategies for avoiding problems related to such active engagement should be planned via promoting effective channels for communication and supervision. The review also suggests the importance of increasing awareness and motivation toward the problem of youth violence among relevant agencies and stakeholders. While the limited volume and quality of the literature impact on the ability to draw conclusions, the results could be useful for new programs being designed and the ones seeking to be adapted from other contexts.