Abiotic stresses (AbS), such as drought, salinity, and thermal stresses, could highly affect the growth and development of plants. For decades, researchers have attempted to unravel the mechanisms of AbS for enhancing the corresponding tolerance of plants, especially for crop production in agriculture. In the present communication, we summarized the significant factors (atmosphere, soil and water) of AbS, their regulations, and integrated omics in the most important cereal crops in the world, especially rice, wheat, sorghum, and maize. It has been suggested that using systems biology and advanced sequencing approaches in genomics could help solve the AbS response in cereals. An emphasis was given to holistic approaches such as, bioinformatics and functional omics, gene mining and agronomic traits, genome-wide association studies (GWAS), and transcription factors (TFs) family with respect to AbS. In addition, the development of omics studies has improved to address the identification of AbS responsive genes and it enables the interaction between signaling pathways, molecular insights, novel traits and their significance in cereal crops. This review compares AbS mechanisms to omics and bioinformatics resources to provide a comprehensive view of the mechanisms. Moreover, further studies are needed to obtain the information from the integrated omics databases to understand the AbS mechanisms for the development of large spectrum AbS-tolerant crop production.