The recent outbreak of the Covid-19 pandemic has reanimated the discussion of socio-economic inequalities and livelihoods’ insecurity across the UK. There is a clear disconnect between policymaking frameworks, macroeconomic theories, and empirical exercises using national and regional statistical data, on the one hand, with the lived experiences of individuals and communities at the local level, on the other. In this paper, we conduct a mixed qualitative and quantitative comparative analysis of eight local areas across four regions in the UK to understand the interconnecting factors affecting individuals’ and communities’ quality of life and prosperity. First, we examine data from the Understanding Society survey between 2009-2018 for the same eight local areas in order to explore individuals’ lived experiences. Second, we examine the eight case study areas across a series of datasets and indices at the local authority (LA) and lower-local super output area (LSOA) levels using an integrated analytical framework based on life outcomes, life opportunities and life together (LOOT). This research approach allows us to gain a better understanding of the main drivers of intra-regional variation and its consequences for macroeconomic policy.