The soil-structure interaction is commonly overlooked in seismic analyses of buildings. However, its omission may lead to an overestimation of seismic performance, especially in the context of complex heritage buildings of significant importance. This study focuses on the seismic performance of the Mosque-Cathedral of Cordoba (Spain), a UNESCO World Heritage Site representing the evolution of Islamic Architecture in the Iberian Peninsula since the VIII century. The building is situated in an earthquake-prone area in the southern Iberian Peninsula, constructed over soft alluvial soil. This research introduces a novel aspect by considering soil-structure interaction in the seismic analysis, particularly focusing on the Abd al-Rahman I sector, the most aged portion of the structure. A finite element model has been developed and calibrated using in situ testing. Nonlinear static analyses were conducted to assess the soil-structure interaction effects on the seismic performance of this sector. The findings reveal potential severe damage to certain parts of the building. It is noteworthy that the presence of alluvial strata amplifies the seismic action, and the results demonstrate a notable worsening when accounting for soil-structure interaction effects.