From Shared Mechanisms to Precision Breeding: Engineering Cold and Drought Cross-Tolerance in Crops.

Low temperature and drought are among the most pervasive abiotic stresses limiting crop productivity worldwide, and their frequent co-occurrence or alternation imposes compounded constraints on agricultural sustainability. Increasing evidence supports cross-tolerance, whereby exposure to one stress enhances resistance to another, as an emergent property of shared signaling networks and integrative regulatory layers. In this review, we summarize recent advances in understanding cold-drought cross-talk, from early stress perception and secondary messengers to hormonal coordination via abscisic acid, transcriptional reprogramming centered on dehydration responsive element binding protein/C repeat binding factor (DREB/CBF) modules, and longer-term regulatory memory mediated by chromatin remodeling and biomolecular condensates. Importantly, we further discuss how these mechanistic insights can be translated into precision breeding strategies, including genome editing, allele mining, and backcross-assisted introgression, to accelerate the development of crop varieties with stable multi-stress tolerance. Finally, we highlight future directions for integrating multi-omics, high-throughput phenotyping, and data-driven approaches to enable efficient molecular design breeding for complex stress environments.