Important links between dietary patterns and diseases have been widely applied to establish nutrition interventions. However, knowledge about between-person heterogeneity regarding the benefits of nutrition intervention can be used to personalize the intervention and thereby improve health outcomes and efficiency. We performed a systematic review of cost-effectiveness analyses (CEAs) of interventions with a personalized nutrition (PN) component to assess their methodology and findings.A systematic search (March 2019) was performed in 5 databases: EMBASE, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar. CEAs involving interventions in adults with a PN component were included; CEAs focusing on clinical nutrition or undernutrition were excluded. The CHEERS checklist was used to assess the quality of CEAs.We identified 49 eligible studies among 1792 unique records. Substantial variation in methodology was found. Most studies (91%) focused only on psychological concepts of PN such as behavior and preferences. Thirty-four CEAs were trial-based, 13 were modeling studies, and 4 studies were both trial- and model-based. Thirty-two studies used quality-adjusted life year as an outcome measure. Different time horizons, comparators, and modeling assumptions were applied, leading to differences in costs/quality-adjusted life years. Twenty-eight CEAs (49%) concluded that the intervention was cost-effective, and 75% of the incremental cost-utility ratios were cost-effective given a willingness-to-pay threshold of $50 000 per quality-adjusted life year.Interventions with PN components are often evaluated using various types of models. However, most PN interventions have been considered cost-effective. More studies should examine the cost-effectiveness of PN interventions that combine psychological and biological concepts of personalization.