Micronutrient deficiencies, particularly iron (Fe) and zinc (Zn), in human diets are affecting over three billion people globally, especially in developing nations where diet is cereal-based. Wheat is one of several important cereal crops that provide food calories to nearly one-third of the population of the world. However, the bioavailability of Zn and Fe in wheat is inherently low, especially under Zn deficient soils. Although various fortification approaches are available, biofortification, i.e., development of mineral-enriched cultivars, is an efficient and sustainable approach to alleviate malnutrition. There is enormous variability in Fe and Zn in wheat germplasm, especially in wild relatives, but this is not utilized to the full extent. Grain Fe and Zn are quantitatively inherited, but high-heritability and genetic correlation at multiple locations indicate the high stability of Fe and Zn in wheat. In the last decade, pre-breeding activities have explored the potential of wild relatives to develop Fe and Zn rich wheat varieties. Furthermore, recent advances in molecular biology have improved the understanding of the uptake, storage, and bioavailability of Fe and Zn. Various transportation proteins encoding genes like YSL 2, IRT 1, OsNAS 3, VIT 1, and VIT 2 have been identified for Fe and Zn uptake, transfer, and accumulation at different developing stages. Hence, the availability of major genomic regions for Fe and Zn content and genome editing technologies are likely to result in high-yielding Fe and Zn biofortified wheat varieties. This review covers the importance of wheat wild relatives for Fe and Zn biofortification, progress in genomics-assisted breeding, and transgenic breeding for improving Fe and Zn content in wheat.