Global agriculture faces significant challenges due to climate change, limited arable land, population growth, and various abiotic and biotic stresses influencing crop production. Abiotic stresses such as drought, salinity, high and low temperatures, and nutrient deficiencies disrupt essential biochemical and physiological processes in plants. Biotic stresses from viruses, bacteria, fungi, nematodes, insects, and weeds cause substantial pre- and post-harvest losses. To ensure food security, it is crucial to develop crop varieties resistant to these stresses. Recent advancements in omics technologies, coupled with big data analysis and machine learning, have enhanced our understanding of plant stress tolerance mechanisms. Omics approaches facilitate high-throughput screening of germplasm, identification of key traits, and selection of stress-resistant individuals using genetic, transcriptomic, proteomic, and metabolomic data. Advanced bioinformatics and specialized databases provide extensive insights into stress-responsive metabolic and signaling pathways, as well as tolerance genes to plant stress. Furthermore, genetic engineering techniques hold significant promise for developing stress-resistant crops. This chapter explores how omics-based methods identify stress tolerance pathways and genes, and highlights genetic engineering efforts leveraging these genes to enhance crop resilience.