In recent years, culture has been addressed as a key component of integrated approaches to local development planning. In this context, it has been systematically combined with institutional and social aspects of local planning strategies and in support of local innovation/creativity systems. However, the articulation of these integrated approaches inhibits a wide typology of context-specific actions in European cities adopting different patterns of promoting culture as an innovative dimension of spatial planning. At the same time, recent discussion in the field suggests the adoption of more holistic frameworks that equally address the role of culture with differentiated aspects such as physical renewal, social relations and governance networks, hence recognising the integrated character of culture-driven interventions and explaining hindering development factors. The present paper aims to elaborate on the importance of such a holistic framework by testing its aspects in the context of the Piraeus Avenue area in Athens (Greece) and the (short-term and fragmented) emanating of developmental policies in support of the creativity and innovation that exist in this locality. The research focuses on the impact of cultural interventions in the Piraeus Avenue area in terms of the building of territorial efficiency, territorial quality, territorial identity and territorial capacity. In parallel, the research addresses the role of demographic and socio-economic parameters in this regard. To address these research aim issues, desktop research together with ten (10) semi-structured interviews with local stakeholders were conducted. Results indicate several positive impacts in the area mostly regarding spatial quality. However, in relation to territorial capacity building, a key finding is the need for activation towards building complementary uses and activities with other types of local stakeholders with accentuated decision-making powers. The research findings can serve to inform policy-making by identifying best practices and key challenges in the formulation of a holistic impact assessment framework towards culture-based spatial development planning in the European space.