<p>Hunger, malnutrition, and climate change (CC) are the prime concerns impacting a substantial fraction of the world’s population. Wheat is one of the notable staple foods imperatives for supporting global food and nutrition security. But wheat production contrarily influenced by CC with the habitual episodes of stresses like water deficit, extreme temperatures, excess and deficiency of nutrients and elevated salts, which compels wheat to be more susceptible to pest and disease occurrence, leads to reduce quality and production potential. In wheat breeding, problems need to be address like nutritional improvement which involves enrichment in protein content, increased micronutrient levels like iron and zinc, vitamins bio-fortification, and resilience to unfavourable conditions. Therefore, it is indispensable to comprehend the molecular and genetic control in different aspects of plant growth and development. Traditional breeding and modern biotechnological approaches have been instrumental in improving wheat’s nutritional quality and resilience to environmental stresses. Advances in genetic engineering, CRISPR-Cas gene editing, and molecular marker-assisted selection are accelerating the development of wheat varieties with superior nutritional profiles and stress tolerance. Integrating omics approaches with traditional breeding and leveraging insights into wheat’s molecular responses can open new avenues in the breeding program of wheat for both food and nutrition security, contributing to sustainable agriculture and resilience against climate change. This review will summarize the current information and strategies for the advances in breeding and molecular biology in wheat for improving multiple stress and enriching nutrient profiles.</p>