Masonry structures are among the most prevalent building types worldwide, many located in areas prone to earthquakes. Understanding their seismic strength and vulnerability is essential. However, modeling these structures poses a challenge due to the complexity of accurately representing masonry walls while maintaining computational efficiency. Consequently, for seismic assessment, improving numerical methods is essential to characterizing masonry within 3D buildings. This paper introduces a methodology that derives effective masonry properties by performing numerical analyses (compression, tensile, and shear tests) on representative volume elements. These analyses use a damage model calibrated with experimental data from masonry units, mortar, and piers to obtain average elastic and inelastic characteristics. The derived properties are then used in a macro-modeling approach that simulates both in-plane and out-of-plane behavior and damage mechanisms while minimizing computational costs. The proposed method is validated through experimental data and applied to real case studies in Cuenca, Ecuador.