<p>The Global Report on Food Crises highlights the immediate requirement for sustainable food solutions in response to a 34% surge in severe food insecurity worldwide. Millets, being ancient grains rich in imperative macro and micro nutrients, have emerged as a crucial element in ensuring food security. Millets can survive adverse environmental conditions such as drought and salinity stress and boost productivity. Hence, millets are a feasible agronomic choice in the contemporary era. Application of selenium and zinc has improved the salinity stress through augmentation of antioxidants like proline, regulation of sodium transporter, ascorbate–glutathione cycle, and morphological traits. Further, genome sequencing identifies candidate genes for agriculturally significant traits and detects crop plant genetic variability. However, the genetic advancement of millets using biotechnological tools such as Quantitative trait locus (QTL) mapping, marker-assisted selection, and breeding is crucial to improve productivity and nutritional security. These techniques have been found to improve resilience to abiotic stresses in foxtail, pearl, and finger millets. Further, an integrated omics approach, including transcriptomics, proteomics, is a potential pathway to develop phenotypes to mitigate the response to environmental stress like drought, salinity, and heat, and to make significant contributions towards the establishment of sustainable and resilient food systems and nutritional security. The application of machine learning can help in the application of genomics and breeding approaches with more precision. The review integrates and emphasizes the role of biotechnological, genomic, and computational-driven tools like machine learning in millet physiological and genetic improvement in the face of climate change.</p>