Maize (Zea mays L.) is one of the most widely cultivated crops globally, making significant contributions to food, animal feed, and biofuel production. However, maize yield is greatly affected by various climate and soil factors, and it faces hindrances due to abiotic stresses, such as drought, salinity, extreme temperatures, and cold conditions. In confronting these hurdles, the field of crop breeding has transformed thanks to high-throughput sequencing technologies (HSTs). These advancements have streamlined the identification of beneficial quantitative trait loci (QTL), associations between markers and traits (MTAs), as well as genes and alleles that contribute to crop improvement. Presently, well-established omics techniques like genomics, transcriptomics, proteomics, and metabolomics are being integrated into maize breeding studies. These approaches have unveiled new biological markers can enhance maize’s ability to withstand a range of challenges. In this chapter, we explore the current understanding of the morpho-physiological and molecular mechanisms underlying maize resistance and tolerance to biotic and abiotic stresses. We focus on the use of omics techniques to enhance maize’s ability to withstand these challenges. Moreover, it emphasizes the significant potential of integrating multiple omics techniques to tackle the challenges presented by biotic and abiotic stress in maize productivity, contrasting with singular approaches.