Assuming that settlement morphologies and landscape structures are the result of economic transformations, the present study illustrates a statistical framework investigating metropolitan growth due to the inherent changes in landscape configurations vis à vis socio-demographic functions. Focusing on the evolution of their spatial drivers over time, metropolitan development was studied by adopting land parcels (or ‘patches’, as they are referred to in the ecological literature) as the elementary analysis unit—with the individual surface area and a specific shape indicator as the dependent variables and background socioeconomic attributes as predictors of landscape change over time. We specifically ran a Multiscale Geographically Weighted Regression (MGWR) testing the spatial dependence of the size and shape of landscape parcels on a vast ensemble of socioeconomic factors in a dense region (metropolitan Athens, Greece) with natural landscapes exposed to increasing human pressure. To investigate the spatial direction and intensity of the settlement expansion and landscape change, local regressions using the parcel area and fractal index (perimeter-to-area ratio) as the dependent variables and the elevation, distance from selected economic nodes, transport infrastructures, and natural amenities as the predictors were run separately for 1990 and 2018, representative of, respectively, a mono-centric configuration and a moderately polycentric organization of economic spaces. In a strictly mono-centric setting (1990), the parcel size showed a linear dependence on the distance from business districts, elevation, and wealth. Changes in the relationship between the parcel size and spatial (economic and non-economic) drivers may suggest a latent process of settlement de-concentration, and a possible shift toward polycentric development (2018), as documented in earlier studies. By integrating socioeconomic and ecological dimensions of landscape analysis and land evaluation, the empirical results of this study outline the increased complexity of dispersed landscape structures within dense metropolitan regions and along urban–rural gradients in Europe.