In this study an ancient fresco (Incoronazione dell'Assunta, 15 th century) in the Santa Maria di Collemaggio Church (L'Aquila, Italy) containing real damage due to the earthquake of April 2009, which seriously damaged the structure, was inspected by active InfraRed Thermography (IRT) and Near-InfraRed (NIR) Reflectography. On the other hand, the fresco's condition prior to the earthquake was analyzed by Electronic Speckle Pattern Interferometry (ESPI) and Digital Speckle Correlation (DSC). Thermographic inspection data was processed using Principal Component Thermography (PCT) and Pulsed Phase Thermography (PPT), in order to improve the signature of the defects and to reduce the impact of non-uniform heating and emissivity variations due to the painting's pigments. This work also shows that the integration of the non-destructive techniques mentioned above, constitutes an interesting alternative for the in situ inspection of frescoes without impairing their integrity. On the sidelines of the discussion are also reported further analysis by IRT and Ground Penetrating Radar (GPR), which helped to fill gaps in the construction history of the original Church.