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 during drought-stress adaptation, 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 architectural features for the yield and drought-stress adaptation of major cereal crops as determined by quantitative genetics and genomics approaches. Further, we compile the root-related drought-responsive quantitative trait loci (QTL)/genes in cereal crops including their inter-species comparisons 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 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.