Abstract : Genetic polymorphism of the fat mass and obesity-associated (FTO) gene, i.e., rs9939609 and rs1121980, was previously thought to be responsible for the pathophysiologies of obesity, metabolic syndrome, and cardiovascular disease (CVD). No strong association of the polymorphisms with vascular properties like transluminal diameter and coronary artery anatomy in populations has been reported despite numerous previous studies. To critically evaluate the interaction of FTO gene polymorphisms with cardiovascular/metabolic events, coronary artery morphology, and demographic diversity at the tertiary level. Systematic searching in PubMed, Embase, Web of Science, Scopus, and Google Scholar up to July 2025. 1,265 records were searched, and 33 studies were screened and evaluated in full-text evaluation, of which 25 studies were included in the meta-analysis. Exposure characteristics, including SNP variant, endpoint, ethnicity, and type of genotyping, were defined. Statistical power in studies was estimated using Quanto software. Pooled odds ratios (OR) and their 95% confidence intervals (CIs) were calculated from the random-effects model. Subgroup analysis by ethnicity, outcome group, and study quality was conducted. Meta-analysis identified FTO rs9939609 risk allele A to be strongly related to CVD risk (pooled OR = 1.29, 95% CI: 1.15–1.44, p < 0.001). The association was consistent in European (OR = 1.33), East Asian (OR = 1.24), and South Asian individuals (OR = 1.21). In the subgroup analysis, the augmented effects were in the combined endpoint obesity-CVD studies and TaqMan genotyping. FTO alleles were associated with transluminal narrowing reported in isolated individual trials, a majority of which were among obese CAD patients. There was no homogeneous socioeconomic context report, but combined data were given for possible gene-environment interaction with vascular anatomy. FTO gene polymorphisms, and particularly rs9939609, have been linked with cardiovascular risk and may influence coronary artery structure, particularly in metabolically vulnerable individuals. Gene screening within the process of CVD risk stratification, particularly in demographically heterogeneous practice, is justified by the findings.