In the context of the multiple challenges generated by the transition to a green and digital economy, the intensification of globalization, and the cumulative impact of recent economic and health crises, analysing the interactions between economic development, innovation and sustainability has become a priority for both academia and policymakers. Within this framework, this chapter aims to investigate, through a rigorous econometric approach, the determinants of sustainable economic performance in the EU, with a focus on identifying the mechanisms through which investments in human capital, digital infrastructure, and innovation can contribute to increasing competitiveness and reducing regional disparities.