The present study demonstrates scientific procedures applied to study mural paintings in two Graeco-Roman tombs of El-Muzzawaka, Dakhla Oases, Egypt. First, a series of analytical methods was applied to determine the chemical and mineralogical composition of pigment and plaster samples collected from the studied tombs. The analyses were performed by means of digitalized optical microscopy (OM), polarized light microscopy (PLM), scanning electron microscopy attached with X-ray microanalysis detector (SEM−EDS), X−ray diffraction analysis (XRD), and Fourier transform infrared spectroscopy (FT−IR). Analyses of the pigment samples revealed Egyptian blue, Egyptian green, green earth, black magnetite, and red/yellow ochres. The paintings were applied on a coarse plaster layer made of gypsum, anhydrite, calcite, and quartz. The preparation layer was made of two phases of calcium sulphate (gypsum and anhydrite). Further, the detection of an organic binder, of gum Arabic, confirms the application of tempera technique. The results showed that the bed rock samples contain variable amounts of quartz, anhydrite, montmorillonite, kaolinite, gypsum, and sodium chloride (halite). In situ observations showed several deterioration forms on the studied mural paintings. The destructive climatic condition of the region and the defects of the rock structure have contributed seriously in the deterioration process. Based on experimental tests, multi restoration procedures were applied in form of cleaning, reattaching paint flakes, applying injection grouts to detached layers, reconstruction of missing parts in the plaster, repair of wide-open cracks, and final protective consolidation of the painted surfaces. Further, recommendations to minimize any future damage were discussed.