The Resurrection of Christ by Piero della Francesca (about 1460) at Sansepolcro (Italy) is a masterpiece in the development of painting. This mural painting was realized on a brick wall (15 cm thick) placed in a different place as it is today. Shortly later, the painting was moved by means of a transport to solid-wall and placed against a pre-existing wall (60 cm thick), where it is today, erecting against this wall a counter wall (15 cm thick) where the mural painting wall-panel (225x200 cm) had been inserted. Sansepolcro area presents a strong historical seismicity (six earthquakes > VII MCS in the last 1000 years), which caused several damages to buildings; moreover in the IIWW the Nazi retiring blasted some edifices causing local vertical rebound up to 1g. For safeguarding the painting from seismic hazard, the Sansepolcro Municipality supported studies regarding the structural behaviour of the hall where the Resurrection of Christ mural painting is. Type and characteristics of the masonries constituting the museum hall and the wall where the mural painting is placed were defined by means of GPR, ultrasonic and micro-endoscopies. These studies outlined a crack pattern subdividing the wall into more vertical panels, the mural painting resulting inserted in the middle of the central panel, but free to move independently thanks to soft link between the mural painting solid-wall-panel and the surrounding masonry. This wall also has a soft link with the lateral walls. A 3D FEM of the museum was built using the data obtained from the investigations on the masonries. Imposing to the FEM the constraints deriving from in situ dynamic tests, we obtained a fine tuning of the 3D FEM and a reliable reproduction of the 3D dynamic behaviour of the building suitable to describe the real motu proprio of the structure and the contribute by the single walls. In detail, the main movement of the wall supporting the mural painting is oscillatory on the wall plane. Wall soft connections and dynamic behaviour explains because the Piero della Francesca's Resurrection of Christ mural painting remained unharmed, despite the numerous seismic events occurred in the area in the past centuries.