Unreinforced masonry buildings show high vulnerability to seismic loading, especially in the out-of-plane direction. Two-way spanning walls are characterized by effective restraints at at least one lateral side of the wall. Their seismic performance under out-of-plane loading has been studied in the literature for walls without openings or with one opening, but it lacks understanding in case of multiple openings. This study presents an engineering approach to calculate the out-of-plane capacity of two-way spanning walls with two openings. Five wall configurations were analysed via non-linear pushover analyses, and crack-pattern evolution tracked. A methodology was proposed which involves dividing the wall into panels whose performance is assessed separately. The division is based on the crack propagation observed in the numerical simulations. Two panels are defined as the wall portions comprised between a side support and an opening which are classified and analysed as three-sided supported walls. Another component corresponds to the wall portion between the two openings and is analysed as a one-way spanning wall. The assessment of the individual panels is based on formulations provided in the Dutch guidelines NPR-9998:2020 which show that the one-way spanning wall panel is the governing one, which is further proved by the analytical calculations.