The concepts of resistance to unforeseen disasters and rapid post-disaster recovery of historic cities are necessary due to the earthquakes that have profoundly influenced their evolution. The improvement of this property strongly depends on the effectiveness of the preventive tools. In this work, an operational framework for the resilience assessment of a historical city characterized by high cultural and historical elements is developed, which corresponds to the main contribution of this research. The research includes multicriteria analysis based on the in-depth knowledge of the city’s historical development, the study of the effects of past earthquakes, structural vulnerability analysis of pombalino buildings, architectural types and socio-economic aspects. The aim is to obtain the necessary elements to guide an aware plan for improving resilience and the reduction of vulnerability through a GIS tool aimed at preventing and defining urban intervention priorities. The framework proposed is applied to Lisbon downtown.