Effective decision-making in tourism destinations relies significantly on employing suitable indicators for policy design and impact evaluation. However, the adoption of sustainability-focused indicators remains constrained in the field of cultural tourism. The purpose of this research is to provide decision-makers with an extensive array of criteria and indicators, enabling informed decision-making, policy formulation, and impact assessment tailored to the distinctive attributes encountered in European destinations. Based on the synthesis of existing approaches, and in co-creation with 21 European tourism destinations, an indicator-based framework is proposed, structured around the environmental, economic, social, cultural, resilience, and characterization domains. The results are particularly novel in the resilience and cultural domains, related to the recovery from crisis impacts, but also to the enhancement of digital approaches, as well as the preservation and promotion of cultural heritage towards a more hospitable destination. Moreover, the involvement of stakeholders incorporating real-case scenarios allows this research to bridge the gap between theoretical constructs and practical application. The indicator-based framework resulting from this research will provide stakeholders with assistance in assessing and comparing the impacts of cultural tourism on their destinations and, thence, help them acquire knowledge on cultural resource management, contributing to a more sustainable, responsible, and balanced impact.