The goal of this research proposal is to re-examine the nexus of social, economic and spatial inequalities in the EU, the various typologies and the arrangements and mix of policies addressing them, in the light of emerging and highly interacting mega-trends and challenges, threatening to increase pressures and make policy choices even more difficult. As new and older drivers of change are projected to create a rather unfavorable environment for balanced growth and socio-spatial resilience, this research will focus on the analysis of policy responses, aiming to make them more pro-active, inclusive and effective. The novel contribution of the proposed research project lies on a holistic and integrated approach that relates in an interactive way drivers to outcomes and levels of aggregation. The aim is to detect, model and map the interdependence among drivers of inequality and outcomes (including circular causality) in a multi-level, poly parametric context with specific tailor-made policy recommendations.