The regionalization of Romania is a subject that has been intensely debated over the past two decades and a half both in the press and in some scientific papers and events. After the 1992 census, territorial regionalization became a statistical reality that was recorded in the first database of regional directories. Subsequently, this was confirmed by the accession to the European Union (EU) and remained valid, and Romania is now divided statistically into eight regions grouped into four macroregions. In this article, the authors propose several optimization criteria and variants for grouping regions in macro-regions and analyze the current statistical viability of indicators that can provide optimized statistical grouping. Finally, any macro-regionalization solution would be considered optimal with respect to the variants exposed, the decision must be based on rigorous statistical data and information.