In this paper, chemical and structural studies of medieval wall paintings in Ocre (L’Aquila, Italy) are presented. During the latest restoration campaign, non-destructive (Near-Infrared Reflectography and Infrared Thermography) and micro-invasive (Nuclear Magnetic Resonance, Fourier Transform Infrared Spectroscopy, μ-Raman, Scanning Electron Microscopy with X-ray Microanalysis, X-Ray Diffraction, X-Ray Fluorescence, Optical Microscopy, Mass Spectrometry, Thermogravimetry) analyses were performed in order to determine the detachments of wall surfaces and the characterization of original and restoration materials. Data integration allowed to reconstruct the conservative history, the execution techniques and the conservation problems of the artefact, as well as to assess the effectiveness of restoration activities adopted. The combined use of physical and micro-chemical techniques proved to be effective for an in-depth study of materials stratification of paintings.