Urban heat vulnerability poses significant and escalating risks, especially in rapidly urbanizing metropolitan areas such as Istanbul. This study introduces an advanced, spatially explicit framework—the Surface Urban Heat Island Vulnerability Index (SUHI VI)—to accurately quantify and map neighborhood-level heat vulnerability across the Istanbul metropolitan region. The SUHI-VI integrates thirteen carefully selected variables spanning exposure (e.g., land surface temperature, impervious surface ratio), sensitivity (e.g., poverty rate, elderly and young population ratios, illiteracy rate), and adaptive capacity (e.g., tree canopy height, vegetation indices, access to green spaces, healthcare facilities, and income levels). The methodological innovation lies in employing a supervised Principal Component Analysis (PCA), which aligns component weighting with empirically observed urban heat anomalies, significantly enhancing both interpretability and practical applicability. Spatial modeling techniques including Multiscale Geographically Weighted Regression (MGWR) and Local Indicators of Spatial Association (LISA) revealed pronounced spatial heterogeneity in vulnerability determinants, highlighting central districts like Esenyurt, Bağcılar, and Gaziosmanpaşa as critical hotspots characterized by compounded demographic pressures and infrastructural deficits. Conversely, peripheral districts such as Şile and Beykoz displayed considerably lower vulnerability due to favorable ecological conditions and higher adaptive capacities. A spatially explicit policy matrix was subsequently developed, combining vulnerability levels and diagnostic model uncertainty to prioritize targeted adaptation strategies effectively. This replicable and scalable framework offers a robust decision-support tool for urban resilience planning, providing actionable insights for equitable and climate adaptive urban governance, applicable to other complex metropolitan regions.