Before starting the restoration of an artwork, good practice involves the evaluation of the item healthiness possibly carried out through non-invasive techniques. In the specific case of painting inspection, hyper- and multi- spectral techniques are commonly used to analyze the outer layers (varnish, pictorial, and drawing), while X-ray, tomography, and many others can be employed to investigate its inner structure. Although highly desirable, a single technique providing all the information about a painting is still not available. Thus, it is of great interest to define the analysis’ protocols that could optimally exploit the complementarities of a minimal set of techniques. To this aim, the present paper shows the combined use of the hypercolorimetric multispectral imaging and pulse-compression thermography on a 15th century wall painting attributed to the Italian artist Antonio del Massaro, also known as Pastura, representing the Madonna with the Child and the Saints Jerome and Francis. The capabilities and the complementarities of the two techniques, whose information can also be fused through post-processing, are illustrated in detail in this paper. In addition, a false-colour imaging approach is proposed to improve the readability and analysis of the thermography results.