In recent years, more than 15 high-resolution wheat genome sequences have been made available to the wheat community by the International Wheat Genome Sequencing Consortium and the 10+ Wheat Genomes Project. The wealth of genomic resources coupled with extensive phenotypic information and in-depth multi-omics analyses allows us to understand the intricate relationships between yield potential, seed nutritive and anti-nutritive component accumulation and broad adaptation to abiotic stresses such as drought. Using high-throughput phenomics, proteomics, metabolomics profiling and micronutrient composition analysis, we monitored cultivar-specific variation in the grain composition of nine cultivars from the pan-wheat collection and the underlying mechanism for their ability to cope with moderate drought applied at the stem elongation stage. We showed that significant variations in phenotypic traits in the vegetative and reproductive tissues were primarily manifested in significant changes at metabolome and micronutrient levels in the grain. However, less than 10% of the quantified grain proteome was affected, suggesting a minimal impact of moderate vegetative stress on grain macromolecular composition. Integrated analysis of the multiple -omics datasets revealed that each cultivar employs a mixture of coping mechanisms. These mechanisms are related to stress escape, avoidance and tolerance by plants increasing intrinsic water use efficiency, controlling respiration and increasing photosynthetic activity, which together maintain grain yield and protein composition under water deficit conditions.Detailed analysis of proteins associated with nutrient reservoir activity reveals a potentially novel function of sulphur-rich proteins in abiotic stress adaptation. Our analysis reveals cultivar-specific variations and the impact of moderate vegetative phase drought stress on grain quality, providing insights into bread wheat’s -omics dynamics, including protein accumulations and sub-genome distributions, and valuable resources for wheat improvement beyond the reference genome.