Introduction: Personalized diets based on an individual's genome to optimize the success of dietary intervention and reduce genetic cardiovascular disease (CVD) risk, is one of the challenges most frequently discussed in the scientific community.Areas covered: The authors gathered literature-based evidence on nutritional genomics and CVD phenotypes, our own results and research experience to provide a critical overview of the current situation of using nutritional genomics to tailor diets for CVD prevention and to propose guidelines for future studies and implementations.Expert commentary: Hundreds of studies on gene-diet interactions determining CVD intermediate (plasma lipids, hypertension, etc.) and final phenotypes (stroke, etc.) have furnished top-level scientific evidence for claiming that the genetic effect in cardiovascular risk is not deterministic, but can be modified by diet. However, despite the many results obtained, there are still gaps in practically applying a personalized diet design to specific genotypes. Hence, a better systemization and methodological improvement of new studies is required to obtain top-level evidence that will allow their application in the future precision nutrition/medicine. The authors propose several recommendations for tackling new approaches and applications.