According to the published European public health policies, emphasis should be given on the identification of high-risk areas, in terms of both Cardiovascular Diseases (CVDs) incidence, as well as of its main clinical risk factors. Thus, we aimed to investigate: (a) the geographical variability of the sex and age-specific 10-year incidence of CVDs and its clinical risk factors in the Athens metropolitan area, the most urbanised city in Greece accounting for about 35% of the total Greek population, and (b) the spatial heterogeneity of the association between the main clinical risk factors and the 10-year CVD incidence at an aggregated level. Data regarding the 10-year CVD incidence (% of population in each municipality with any CVD after the 10-year period), as well as the prevalence of the risk factors (obesity, hypertension, diabetes mellitus, hypercholesterolaemia; expressed as % of population in each municipality) were provided by the ATTICA epidemiological study for 2020 individuals found during the 10-year follow-up with complete data for locality geocoding. Socio-economic, demographic, and environmental characteristics for each municipality of the Attica region, were obtained from official national and international databases. A local statistical modelling approach, namely the Geographically Weighted Regression, was implemented in order to investigate the associations at a local level and therefore give emphasis on the design of more effective public health programs, taking into account the special characteristics of each area. Hypercholesterolaemia was found to be the most prevalent clinical risk factor in the study area, while higher prevalence for all the risk factors were presented in areas of lower socioeconomic status (SES), where a significantly higher number of new CVD cases in the decade were detected as well. 10-year CVD incidence was also found to be significantly elevated in areas characterized by worse health status in terms of the risk factors’ prevalence, while the sex and age- specific CVD incidence rates were found to be differently affected by these factors. Interestingly, despite the fact that CVDs are acknowledged as a man’s disease, areas of higher (South & North) and moderate (East) SES were found to be characterized by higher CVD incidence rates in females, while in areas of lower SES (West), higher CVD incidence rates were found in males. In line with the current European policy, the identification of areas where the intensity of the studied associations is stronger, can be considered a crucial methodological aspect for the design and implementation of more effective CVD prevention programs at the community level.