Considering the amount of uncertainty involved, the seismic analysis of masonry buildings remains an important and challenging task for heritage preservation initiatives. San Giovannello Church, located in Gerace (Southern Italy) is selected as a case study and investigated in this article. To address the seismic response of this masonry church, a preliminary study utilizing advanced non-linear dynamic simulations was carried out. A finite element model was conceived based on a detailed geometry obtained on a laser scanner survey of the church. To simulate the non-linearity of the masonry construction, the Concrete Damage Plasticity model (CDP) was adopted as a common approach for the masonry material. The mean values of the mechanical properties were extrapolated from the existing literature, matching the construction typology of the encountered structure. The seismic action for the analyses consists of a set of ten natural two-component ground motions recorded on rock site conditions. This set was selected based on the results of seismic hazard disaggregation computed at the spectral period and return period of interest. Additionally, to account for soil effects, one-dimensional Site Response Analysis (SRA) was carried out, while topographic effects were incorporated using amplification factors from previous studies. The out-of-plane and the in-plane failure mechanisms were investigated for the four top representative points of the church, in terms of maximum transient horizontal displacement. As expected for typical historical masonry buildings, the results show a high seismic vulnerability, exhibiting widespread, and severe damages. The results also highlight potential vulnerabilities and provide a basis for further assessment of the church’s seismic fragility.