The Italian National Strategy for Inner Areas stresses the importance of improving socio-economic conditions of people as the only way to reverse negative demographic trends in those areas. In this respect, improving quality of life (QoL) may represent a key driver. This work provides a statistical tool to measure existing gaps in QoL levels across Italian NUTS 3 regions, by focusing on inner areas. Being QoL a multidimensional concept, a composite indicator is computed following a non-compensatory approach: the QoL Mazziotta-Pareto Index. Firstly, we consider the variability of this indicator across Italy, with respect to the presence of inner areas. This analysis breaks down the supposed negative relationship between QoL and presence of inner areas, which the paper proves to be mostly overlapping with rural ones, by controlling for sub-national structural divides. Secondly, spatial aspects make the picture more complex. Neighbourhood affects QoL at local level and through 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, locked-in paths among neighbouring regions can influence the effectiveness of place-based policies.