Two mural paintings located in the “House of Garden”, recently excavated in the Regio V of the archaeological site of Pompeii (Campania, Southern Italy), were studied. The mural paintings are in room 3 of the house. The first is a large-scale scene representing Venus with a male figure (possibly Adonis or Paris since he has a bow) and Eros, while the second one is a fine female portrait, perhaps depicting the domina of the house. All analyses were carried out in situ, using a new non-destructive methodology based on the acquisition of good-resolution visible images and the chemical information obtained by a portable hand-held X-ray fluorescence device. All data were statistically combined using a computer program, named SmART_scan, obtaining maps of the distribution of the elements (or compounds) on the painting. Visible induced luminescence (VIL) was used to confirm the presence of Egyptian Blue. The study performed on the two mural paintings allowed us to identify the various pigments used and to determine the presence of degradation products, such as soluble salts and a violet-black discoloration that, in the first painting, has modified some of the original colours, producing substantial changes in the interpretation of the figures. The results of the work show that the SmART_scan methodology, coupled with an X-ray fluorescence device and a good-resolution visible image, is a valid tool for obtaining the spacial distribution of each element and often of the pigments as combination of them, on large surfaces in a short time and at low cost.