The seismic vulnerability of the masonry built heritage in mainland Portugal is a pressing concern, despite an absence of major earthquakes in recent times. This concern is particularly pronounced in the Metropolitan Area of Lisbon with high exposure, which experienced a devastating earthquake in 1755 (MW = 7.8). Consequently, it is imperative to undertake a thorough characterization of the seismic fragility and vulnerability of this region, along with an evaluation of potential mitigation strategies, such as seismic retrofitting. Once given an insight into the characterization of the fragility of the Metropolitan Area of Lisbon, the paper delves into exploring the efficacy of masonry strengthening interventions in reducing vulnerability and fragility. A meso-modeling strategy was used within the Applied Element Method to predict the seismic behavior of representative masonry archetypes and simulate the impact of strengthening interventions on building stock. The outcomes of the study are discussed through numerical fragility curves.