Cereal crops such as rice, wheat, maize, sorghum, barley, and millets are staple food sources for more than half of the global population. These crops are frequently exposed to multiple stresses simultaneously or sequentially, including drought, heat, salinity, flooding, and diverse biotic factors such as pathogens and insect pests. Combined stresses typically cause greater yield losses than individual stresses, due to synergistic and often unpredictable physiological and molecular responses. Recent research highlights that plants under multiple stresses exhibit distinct morpho-physiological alterations such as accelerated senescence, impaired photosynthesis, reduced reproductive success, and hydraulic dysfunction. Biochemically, stress-induced accumulation of reactive oxygen species (ROS) is more pronounced under combined stress conditions, requiring enhanced antioxidant responses, osmolyte biosynthesis, and metabolic reprogramming. Hormonal crosstalk, especially among ABA, JA, SA, and ethylene, emerges as a central integrator of stress signals. At the molecular level, transcription factors such as DREB, NAC, and WRKY families orchestrate transcriptional reprogramming, while QTLs and candidate genes for multi-stress tolerance are increasingly being identified through genomics and phenomics approaches. Despite these advances, breeding for multi-stress resistance remains a formidable challenge due to genotype × environment interactions, trait complexity, and yield penalties under favourable conditions. Integrated breeding strategies, leveraging genomic selection, CRISPR-based editing, high-throughput phenotyping, and agronomic management, are essential to achieve climate-resilient cereals for future food security.