This paper evaluates the improvements in wall paintings diagnostic achievable by the synergistic combination of DHSPI, SIRT and MWR techniques. These innovative portable and non-destructive techniques for in-situ diagnostic were tested in laboratory on mock-ups mimicking the real conditions of wall painting defects (such as detachments, cavities and cracks), and on the frescoes painted by Masolino, Masaccio and Filippino Lippi (between 1422 and 1475) in the Brancacci Chapel in the church of Santa Maria del Carmine in Florence, Italy. This research activity was part of the Brancacci Chapel diagnostic and monitoring project, where the assessment of the state of conservation is a mandatory prerequisite for planning the subsequent restoration work. In common practice, restorers make the preliminary evaluation on the state of conservation of the wall paintings by visual and tactile inspection, without the use of any special scientific instrumentation. Cracks, cavities, lack of material, detachments, out-of-plumb and deformation of (non-)structural elements are reported in a condition report to document the state of conservation at a given point in time. In particular, the detachments are recognized by the tap test, but this is a discretionary and highly subjective method. Thus, there is a strong demand for the development of a portable and non-destructive approach that refines this preliminary survey with objective data. Here, we present the results produced by the combination of MWR (useful for the dimensional characterization of hidden defects in the wall) and DHSPI-SIRT to identify the extent of deformations induced by thermal stimulus, providing an objective confirmation of the preliminary investigation performed by restorers, in which the detachments were indicated as “stable”, “not very stable” and “unstable”, i.e., close to falling. The integrated use of these techniques in situ, supported by a laboratory study on ad-hoc prepared mock-ups, proved to be suitable for a quantitative evaluation of damage risk to guide restoration strategy accordingly.