Culture-led urban regeneration is recognized as an effective approach for revitalizing distressed urban areas, yet its implementation in metropolitan contexts faces multidimensional complexities. The primary objective of this research is to explore and identify the challenges of culture-led urban regeneration in District 16 of Tehran from the perspective of urban experts and policymakers. Employing a qualitative methodology, data were collected through in-depth interviews and subsequently analyzed using thematic analysis. The findings revealed that the barriers to culture-led regeneration are categorized into three main themes: first, the "political economy of space and the failure of collaborative governance," which stems from institutional fragmentation, speculative approaches, and a lack of integrated policymaking; second, the "reproduction of spatial inequality and socio-cultural alienation," manifesting through the risks of gentrification, commodification of heritage, and erosion of social capital; and third, "morphological decline and the collapse of the urban framework," encompassing severe physical limitations, fine-grained parcels, spatial fragmentation caused by macro-arteries, and infrastructural poverty. In conclusion, realizing the objectives of culture-led regeneration in distressed metropolitan areas requires a paradigm shift from reductionist, physical-centric interventions toward institutional capacity building, authentic citizen participation, and balanced infrastructural development based on endogenous local assets, providing significant practical implications for urban planners and policymakers.