Currently, at the end of the programming period 2014–2020 and in the view of the new programming exercise, 2021–2027, knowing where South-Muntenia is positioned on the path to sustainable regional development and how the main determinants can be integrated in regional development policies in order to continuously support the development of the Romanian regions becomes even more important. In this context, the paper aims to evaluate the progress made by the South-Muntenia region towards sustainable regional development for the period 2010–2017 highlighting the main implications for regional development strategies and revealing local initiatives promoting broader sustainable regional development. Thus, more in depth, the paper aims to identify the main determinants of sustainable regional development at the level of South-Muntenia counties using multiple principal component analysis (MPCA), to build an advancement sustainable development index based on panel data for the period 2010–2017 and to reveal the main sustainable development poles at the county level for the year 2017 using hierarchical clustering technique. The empirical results revealed the importance of business environment, public services infrastructure, education, and social protection as main determinants of South-Muntenia sustainable regional development. The advancement composite index pointed out that South-Muntenia recorded a slow but continuous advancement in terms of sustainable regional development, almost doubling its performance in these seven years. At the county level, if Prahova, Argeș, and Dâmbovița exhibited a so-called stagnation, Ialomița and Teleorman were still behind, registering an advancement over the period but remained only halfway on the path to sustainable development, while Calarasi and Giurgiu tried to recover the huge gap, registering very low rates of sustainable development index. On the path to regional economic development, the relevance of two main sustainable regional development drivers can be highlighted—a better allocation for active measures with the reduction of unemployment as a target together with a better infrastructure of public services. National, regional, and local administrations play an important role in promoting sustainability in the economic, social, and environmental activities, in a coherent manner. Regardless of the level at which development policies are designed, local, county, or regional, they must take into account and monitor the sustainable development determinants if the ultimate goal is the overall regional development of South-Muntenia.