Aim <p>Social determinants extensively impact human health. Despite the development of global health policies, disparities persist. This study examined the association between demographic, economic, governance, and health indicators and health outcomes across 26 European countries.</p> Subject and methods <p>Data from 2018–2021 were extracted from the World Bank (20 variables) and the Global Burden of Disease (mortality, DALYs, YLL, and YLD). Indices were created by normalizing and averaging variables. In line with the exploratory design, multivariable linear regression models tested the association between indices and health outcomes.</p> Results <p>The health index was the strongest predictor, showing a negative association with overall DALYs and YLLs (<i>β</i> = −1.06) and major noncommunicable diseases, including cardiovascular disease, diabetes, non-alcoholic fatty liver disease, and cancers (<i>β</i> = −0.63 to −1.21). Positive associations were found for gynecological, dermatological, and mental health disorders (<i>β</i> = 0.62 to 1.00), likely due to improved detection in countries with advanced healthcare systems. The governance index showed strong collinearity with the health index and was therefore excluded from regression models. The economic index showed limited associations, including a positive relationship with mental health burden (<i>β</i> = 1.06–1.13) and a negative link with YLDs from digestive diseases (<i>β</i> = −0.81).</p> Conclusion <p>These results underscore the significance of health system capacity and institutional quality as primary drivers of health, surpassing the influence of economic or demographic factors.</p> Graphical Abstract <p></p>