The Italian National Strategy for Inner Areas explicitly draws policymakers’ attention to inner municipalities. It stresses the importance of improving socio-economic conditions of people as the only way to reverse negative demographic trends in those areas. To this respect, improving quality of life (QoL) represents one of the key drivers. Given such an important policy implication, this work provides a statistical tool to measure existing gaps in QoL levels across Italian NUTS 3 regions, by explicitly disentangling urban and inner areas. Nevertheless, QoL is a multidimensional concept, thus a composite indicator is computed following a non-compensatory approach: the QoL Mazziotta-Pareto Index. Firstly, we consider the variability of the comprehensive indicator across Italy, with respect to the presence of inner areas. As a major result, this analysis seems breaking down the supposed negative relationship between QoL and presence of inner areas, which the paper proves to be mostly overlapping with rural ones, when controlling for sub-national structural divides occurring throughout Italy. Secondly, spatial aspects make the picture even more complex. Even the neighbouring space is expected to affect QoL at local level. In particular, by means of both global and local indicators of spatial autocorrelation, groups of NUTS 3 regions sharing similar QoL levels with their neighbours are detected. From a policy perspective, such a locked-in path among neighbouring regions can influence the effectiveness of place-based policies.