Climate change threatens the productivity or stability of global agriculture, particularly the major cereals that serve as global staples (i.e., wheat, rice, maize, barley, sorghum, and millet). The combination of higher temperatures, fluctuating rainfall, salinity, drought, and pest and pathogen pressure significantly undermines agricultural yields and food security. Genome editing technologies, particularly CRISPR/Cas systems, have proven to be transformative tools for developing climate-resilient crops with increased tolerance to abiotic and biotic stresses, improved nutritional quality, and sustainable performance in variable environments. This chapter discusses genome-editing methods and their role in improving cereal crops against the main climatic stress factors, including drought, heat, salinity, elevated CO₂ levels, and pest infestation. Relevant case studies are used to illustrate impressive applications of CRISPR, with a focus on increasing crop yields, improving tolerance to environmental stressors, and enhancing nutritional biochemistry. This chapter focuses on the introduction of the omics/bioinformatics-assisted process of localizing target genes and implementing genome editing in breeding pipelines. This includes off-target effects, delivery methods, regeneration protocols, and regulatory frameworks. The application of genome editing in climate-smart agriculture is therefore key to sustainable grain production and global food security in the future.