Serbia continues to face a significant public health challenge, with cardiovascular mortality (CVM) as the leading cause of death. The spatial distribution of CVM is shaped by a complex interaction of demographic, socio-economic, healthcare, and environmental factors, reflecting deep regional disparities. This study employs a geospatial approach to analyze municipal-level (LAU 1) CVM patterns in 2023, using Geographically Weighted Regression (GWR) modeling to assess localized relationships between CVM and its key determinants. The results reveal distinct spatial variations in the influence of demographic structure, socio-economic conditions, and healthcare accessibility on CVM across Serbia’s 168 municipalities. Through cartographic visualization, the study identifies critical factors driving mortality rates at a local level, providing understanding of compromised health spaces. By highlighting spatial inequalities, this research offers essential insights for policymakers, enabling the development of targeted, place-based interventions to mitigate CVM risks and promote health equity. Addressing these localized vulnerabilities is crucial for designing effective public health strategies that acknowledge Serbia’s diverse geographic and socio-economic landscape. Ultimately, this study underscores the importance of spatial analysis in public health research, laying the foundation for more data-driven, regionally adaptive responses to the burden of cardiovascular diseases.