This thesis provides a comprehensive analysis of the role of cultural tourism on regional economic resilience in South-European EU regions during the COVID-19 pandemic, focusing on both resistance (2020) and recovery phases (2021-2022). The study utilized a sample of 378 NUTS 3 regions and defined cultural tourism through six indicators: world heritage sites, UNESCO intangible cultural heritage elements, national monuments, national intangible cultural heritage elements, museums, and cultural and creative enterprises, as defined by the Horizon 2020 SmartCulTour project. Robust results were obtained using non-spatial (OLS) and spatial (SDEM) regression models, revealing the phase-specific role of cultural tourism. During the resistance phase, cultural tourism tended to negatively impact economic resilience, particularly in relation to national monuments. However, in the recovery phase, all indicators showed significant positive impacts, highlighting cultural tourism’s crucial role in economic recovery. The study also uncovered significant spatial dependencies and heterogeneity in the relationship between cultural tourism and economic resilience. Regions were clustered in two ways: predetermined based on Eurostat’s Territorial Typologies and using a new, original classification by employing thesis data and the spatial regimes approach. Results indicated that cultural tourism made urban regions vulnerable during the shock but was essential for their recovery, especially through physical and creative assets. Intangible cultural heritage was found to be vital for rural and mountain regions, while all cultural tourism indicators were significant for coastal regions. The spatial regimes approach further confirmed spatial heterogeneity, with cultural tourism proving most important for the economic resilience of NUTS 3 regions in Croatia and Greece. The research contributes academically by being the first to explore cultural tourism’s role in regional economic resilience during the COVID-19 shock with a phase-specific and spatially heterogeneous context. In terms of policy implications, it confirms cultural tourism’s direct effects on regional resilience, reaffirming it as a key component of territorial capital for regions. It emphasizes the need for adaptive, phase-specific, and cluster-specific strategies. Policymakers are advised to consider these insights for developing Smart Specialization Strategies, promoting cultural tourism to enhance regional economic resilience.