<p>Orphan crops, underutilized species with regional or local importance, are increasingly recognized for their potential to enhance global food and nutrition security, particularly under climate stress and resource limitations. These crops, often resilient and adapted to marginal environments, offer untapped opportunities for sustainable and diversified agricultural systems. This review synthesizes recent advances in genomic technologies, including next-generation sequencing, genome editing, and marker-assisted selection, which are driving the precision improvement of orphan crops. These tools facilitate the identification and integration of complex traits such as drought tolerance, pest resistance, and enhanced nutritional quality, overcoming long-standing barriers to productivity and adoption. Integration of modern genomics with participatory breeding approaches enables the development of resilient, locally adapted cultivars optimized to smallholder farming systems across Africa, Asia, and Latin America. Despite these advances, challenges remain, including limited genomic infrastructure, underrepresentation in global research agendas, restricted access to sequencing platforms, and inadequate policy and funding support. The review also highlights critical priorities for scaling up, including open-access data sharing, capacity building in low-resource regions, and the formulation of enabling policy frameworks. By supporting genomic innovations with equity-driven strategies and local knowledge systems, orphan crops can be repositioned as cornerstone species in climate-resilient, sustainable, and diversified food systems. Thus, this synthesis emphasizes the transformative potential of genomics to unlock the value of orphan crops and calls for coordinated, cross-sectoral efforts to fully integrate them into global agricultural development strategies.</p>