Exploiting root system variations related to drought stress adaptation using quantitative genetics and genomics approaches has potential in developing resilient varieties of cereal crops. Abstract Cereals are important crops worldwide that help meet food demands and nutritional needs. In recent years, cereal production has been challenged globally by frequent droughts and hot spells. A plant’s root is the most relevant organ for the plant adaptation to stress conditions, playing pivotal roles in anchorage and the acquisition of soil-based resources. Thus, dissecting root system variations and trait selection for enhancing yield and sustainability under drought stress conditions should aid in future global food security. This review highlights the variations in root system attributes and their interplay with shoot architecture features to face water scarcity and maintain thus yield of major cereal crops. Further, we compile the root-related drought responsive quantitative trait loci/genes in cereal crops including their interspecies relationships using microsynteny to facilitate comparative genomic analyses. We then discuss the potential of an integrated strategy combining genomics and phenomics at genetic and epigenetic levels to explore natural genetic diversity as a basis for knowledge-based genome editing. Finally, we present an outline to establish innovative breeding leads for the rapid and optimized selection of root traits necessary to develop resilient crop varieties.