The need for food increased due to population growth and several environmental stresses, including drought stress. To meet this demand, researchers looked for practical and long-term solutions, concentrating their efforts on improving crop plants to ensure sustainable food production. A drought is a bad misfortune for agriculture and for people in general. Drought stress triggers the defense mechanisms that are already present in plants. Crop plants have yielded an abundance of genomic resources, and agricultural studies and crop breeding have been transformed by bioinformatics technologies. This chapter covered the bioinformatics application in crop plant breeding to drought tolerance, highlighting drought stress and bioinformatics, as well as the applications of bioinformatics in agriculture studies and crop plant breeding, in addition to the application of bioinformatics for drought tolerance through metabolomics, proteomics, transcriptomics, genomics, miRNA omics, and phenomics techniques. The detection, management, and control of water deficit or drought stress, the research of physiological processes, and the quick and effective screening, dissection, and validation to comprehend the genetic basis of various characters, genes, and aspects are all made possible by these plant bioinformatics tools. By integrating previous bioinformatics technologies in plant breeding, they could be applied to create novel cultivars resistant to drought stress with high productivity. Plant breeders will have greater access to bioinformatics tools in the future, which requires utilizing them in the field of crop breeding to confront drought and other climate changes to feed the world’s population.