Iron (Fe) and zinc (Zn) are recognised as micronutrients of clinical significance to public health globally. Major staple crops (wheat, rice and maize) contain insufficient levels of these micronutrients. Baseline concentrations in wheat and maize grains are 30 µg/g for Fe and 25 µg/g for Zn, and in rice grains, 2 µg/g for Fe and 16 µg/g for Zn. However, wheat grains should contain 59 μg Fe/g and 38 μg Zn/g if they are to meet 30–40% of the average requirement of an adult diet. Scientists are addressing malnutrition problems by trying to enhance Fe and Zn accumulation in grains through conventional and next-generation techniques. This article explores the applicability and efficiency of novel genome editing tools compared with conventional breeding for Fe and Zn biofortification and for improving the bioavailability of cereal grains. Some wheat varieties with large increases in Zn concentration have been developed through conventional breeding (e.g. BHU1, BHU-6 and Zincol-2016, with 35–42 µg Zn/g); however, there has been little such success with Fe concentration. Similarly, no rice variety has been developed through conventional breeding with the required grain Fe concentration of 14.5 µg/g. Transgenic approaches have played a significant role for Fe and Zn improvement in cereal crops but have the limitations of low acceptance and strict regulatory processes. Precise editing by CRISPR-Cas9 will help to enhance the Fe and Zn content in cereals without any linkage drag and biosafety issues. We conclude that there is an urgent need to biofortify cereal crops with Fe and Zn by using efficient next-generation approaches such as CRISPR/Cas9 so that the malnutrition problem, especially in developing countries, can be addressed.