We report on the XPS analysis of degraded surfaces inside San Pietro Barisano, the rupestrian church carved into the calcarenite rock of ancient Matera, which has been a UNESCO World Heritage Site since 1993. As reported in previous works, the “Sassi” district and the park of rupestrian churches were available as open laboratories for the National Smart Cities SCN_00520 research project dedicated to the sustainable recovery of this remarkable architectural heritage. In that context, XPS functionality was shown to reside in the possibility of analyzing surfaces by feasible sampling, acquiring spectra without any preliminary sample treatment, and processing data using a well-established curve fitting procedure. The obtained results allowed us to identify the degradation products of the investigated surfaces, thus contributing to defining a diagnostic framework for subsequent actions. Accordingly, the samples here considered, collected from the internal wall surfaces of the church, were all analyzed in comparison with the reference calcarenite, and the XPS results were evaluated as a function of local environmental factors and the historical context of the church itself. The final aim was to provide, for each sample, the most representative indicator(s) of biotic and/or abiotic degradation for reliable use, in a multidisciplinary context, in planning care interventions for building heritage.