The objective of this study was to characterize the development regions in Romania and to measure spatial imbalances, starting from the national and the European Union aspiration to promote more economic and social policies adapted to the different regional particularities. For this purpose, we conducted a multifactorial analysis of the sustainability of the development regions in Romania at NUTS II level by constructing a synthetic index of socio-economic development for the regions that appreciate sustainability and have accepted structural and cohesion funds. The multi-criteria synthetic index was obtained by aggregating several sub-indices (economy, health, education, public utilities, and living standards). We used cluster analysis to identify patterns of regional development in Romania over time. For 1998 and 2006, the same cluster structure was obtained. However, due to economic and social changes that occurred after 2006 (negative impact of the global financial crisis as well as the positive impact of EU funds), in 2016, we recorded another structure of clusters, except in the Bucharest-Ilfov region which continues to present a number of unique features. In addition, we show that the polarized regional development model is increasingly strengthening and the network of urban agglomerations needs to be territorially balanced to boost their ability to “export” wealth.