This chapter investigates the potential of a systemic, multi-scalar, data-driven approach to support the definition of strategies and actions related to the development of rural inner areas. The proposed four-step methodological framework aims at managing the complexity of these marginal territories, to enhance the effectiveness of processes of regeneration. The preliminary collection and elaboration of spatial data, including demographic, economic, cultural, environmental input, enables an analysis entailing multi-scalar, multidisciplinary dimensions, integrating information on the value components of the natural, tangible, and intangible cultural heritage, along with the wealth of human and social capital available. This analytic phase brings to the fore the primary features of the identity of rural inner areas, ultimately leading to an operative, holistic vision for engaging local stakeholders in a participatory co-design process. The initial exploration is functional to a subsequent phase of synthesis that focuses on recognizing systemic interconnections, together with active and potential networks, with the aim to select neuralgic nodes that can maximize the impact of regeneration. In this way, the structural remoteness and marginality of rural inner areas is counterbalanced by co-creation with local stakeholders, and activation of physical and narrative interconnections between selected points of interests (POIs) that serve as new polarities (services, functions, infrastructures, etc.) that can enhance accessibility and attractiveness. This perspective opens the way to moving beyond the traditional urban/natural dichotomy, providing new classification models and initiatives of transformation to foster the sustainable growth of rural areas by reconnecting them to the social, cultural, and economic networks of their surrounding territories.