The heritage value of the mixed wood-masonry 18th century Pombalino buildings of downtown Lisbon is recognized both nationally and internationally. The present paper focuses on the seismic assessment of global response and retrofitting of a typical Pombalino building by nonlinear static analyses, performed by the research software Tremuri, which is able to model 3D configurations. The structure is modelled using nonlinear beams for masonry panels, while in case of the internal walls (frontal walls) an original formulation has been developed in order to take into account their specific seismic behaviour. Floors are modelled as orthotropic membrane finite elements: this feature allows to simulate the presence of both flexible and rigid diaphragms, being the first ones more representative of the original state while the second ones of retrofitted configurations. Seismic assessment has been evaluated by applying nonlinear static procedure and comparing the performance of different configurations (by considering various retrofitting strategies). Finally, assuming a lognormal cumulative distribution, fragility curves are obtained to be representative of Pombalino buildings: the most important application of such curves is for seismic risk and loss estimation analyses.