Despite dietary modification is recommended as the first-line therapy for the management of blood pressure (BP), substantial inter-individual variability in BP response to diet persists (1). This may be partly explained by the interactions between genetic and dietary factors, given the multifactorial and polygenic nature of BP (2). To date, no systematic review has synthesised studies of associations using the application of Genome-Wide Association Studies or polygenic risk scores (PRS), and dietary intake in relation to BP. Six databases were searched to identify observational and intervention studies evaluating associations between genetics and dietary factors in relation to BP [including systolic (SBP) and/or diastolic BP (DBP) or hypertension (HTN)]. Of 9,443 studies identified from the search, 28 studies (18 observational, seven intervention, three Mendelian Randomisation studies) were included. Data were independently extracted by two reviewers. Quality assessments were conducted for each included study using the Q-Genie tool (3) and the overall certainty was determined using the Grading of Recommendations Assessment, Development and Evaluation approach(4). Due to heterogeneity across genetic and dietary exposures, results were summarised narratively. Studies predominantly assessed BP-related outcomes, including SBP (14 observational, seven intervention and one Mendelian Randomisation study) and/or DBP (13 observational, six intervention and one Mendelian Randomisation). Sodium (Na) intake (nine studies) was the dietary variable assessed most commonly. While seven of the included studies did not report the dietary assessment method used, they assessed objective urinary Na and K as biomarkers of dietary intake. PRSs constructed using whole genome-wide sequencing were rare (one study). Mixed evidence was identified for gene-Na interactions, whilst higher K intake was associated with lower SBP across five genotypes. Within the food or food group categories, contrasting results were reported for coffee consumption. Interaction of LGR5 (rs1297184) gene variant with alcohol intake was significantly associated with higher DBP among C-allele carriers (β = 0.11). Inconsistent SBP results were reported when assessing interactions between the DASH diet score and four genetic variants. Intervention studies identified several genetic variants associated with increased SBP during high Na diet arms. Individuals with high SBP-PRS and high/moderate sodium-sensitive groups showed greater SBP increases, whereas sodium-resistant individuals exhibited decreases in SBP and DBP when consuming a high Na diet. For HTN risk, evidence for gene-Na interactions was mixed. Two Mendelian Randomisation studies reported higher HTN risk associated with poultry, beef and noodle intakes and alcohol consumption. Overall, substantial heterogeneity across genetic and dietary exposures in the included studies resulted in highly inconsistent evidence and very low certainty for the relationships between genetics and diet on BP-related outcomes. Further research is needed to evaluate relationships using robust methods, such as applying similar phenotypic PRS and validated dietary assessment tools.