Failure analyses require more and more reliable and robust approaches to structural response prediction. This represents a quite complex task to be accomplished especially when dealing with historical or ancient constructions in seismic geographic areas. The paper is aimed at providing approaches to the analysis of buildings alternative to simplified methods usually adopted in professional practice, which do typically involve drastic simplifications of the fabric. The approach allows developing full holonomic non-linear analyses for forecasting the behavior of structural panels present in the structural system, and it results in higher reliability and flexibility than ordinary procedures that are generally adopted in commercial software and are typically based on gross simplifications of the real structure. The presented method allows taking into account the real geometry of the masonry building under analysis, also including a number of elements such as architraves, tendons or reinforcements possibly incorporated into the walls. Besides the consistent improved reliability in performing structural analyses under quasi-static loads, the main potential of the approach is related to the possibility of developing its extension for performing dynamic analyses quite easily.