Population growth, climate change, and limited dietary diversity pose growing threats to food security. This predicament is exacerbated by a small number of staple crops with limited genetic diversity, which constrains their adaptability to diseases, pests, and environmental changes. Orphan crops, with greater biodiversity, nutritional value, and local adaptability, could contribute to overcoming these challenges. Here, we review recent advances in germplasm identification as well as genetic and multi-omics analyses of orphan crops. We further discuss the potential for an integrated approach combining de novo domestication, speed breeding, and AI-empowered phenomics (DSAP) to accelerate the breeding of these species.