Gene–nutrient interactions (GeNuIne) collaboration, a large-scale collaborative project, has been initiated to investigate the impact of gene–nutrient interactions on cardiometabolic diseases using population-based studies from ethnically diverse populations. In this project, the relationship between deficiencies of vitamins B12 and D, and metabolic diseases was explored using a nutrigenetic approach. A genetic risk score (GRS) analysis was used to examine the combined effect of several genetic variations that have been shown to be associated with metabolic diseases and vitamin B12 and D deficiencies, respectively. In Sri Lankan, Indonesian and Brazilian populations, those carrying a high B12-GRS had an increased risk of metabolic diseases under the influence of dietary protein, fibre and carbohydrate intakes, respectively; however, in Asian Indians, genetically instrumented metabolic disease risk showed a significant association with low vitamin B12 status. With regards to nutrigenetic studies on vitamin D status, although high metabolic-GRS showed an interaction with dietary carbohydrate intake on vitamin D status, the study in Indonesian women demonstrated a vitamin D GRS–carbohydrate interaction on body fat percentage. In summary, these nutrigenetic studies from multiple ethnic groups have provided evidence for the influence of the dietary factors on the relationship between vitamin B12/D deficiency and metabolic outcomes. Furthermore, these studies highlight the existence of genetic heterogeneity in gene–diet interactions across ethnically diverse populations, which further implicates the significance of personalised dietary approaches for the prevention of these micronutrient deficiencies and metabolic diseases.