The dissolution of nano-sized Ni3Al-based γ′ precipitates was investigated in the newly developed polycrystalline nickel-based VDM® Alloy 780 at the surface and in the bulk region with in-situ lab-source and synchrotron X-ray diffraction. These studies are important in obtaining a deeper understanding of the strengthening mechanism responsible for the stability and long service lives of such superalloys. We found that the dissolution behavior of the γ′ phase is very similar at the surface and in the bulk region, but small deviations were detected. The dissolution of γ′ starts at around 800 °C and no γ′ was found at temperatures exceeding 970 °C. As a result, the elements Al and Nb, which were bound in the γ′ phase, dissolved into the γ matrix and strongly increased the γ lattice parameter, as their atomic size is larger than the γ-forming elements Ni, Co, and Cr. However, this effect was suppressed in the surface area. A second matrix γ phase was detected at the same temperature range as that of the dissolution of the γ′ phase in the lab-source XRD measurements. The newly formed γ-2 phase had a smaller lattice parameter than that of the initial γ matrix. We propose that the γ-2 matrix phase is a result of high-temperature surface oxidation, which consumes, among other elements, Al and Nb and, therefore, leads to the smaller γ lattice parameter.