jats:titleAbstract</jats:title> jats:pA detailed analysis of the response of as-cast third-generation single-crystal nickel-based superalloy CMSX-10Kjats:sup®</jats:sup> to solution heat treatment (SHT) has been carried out, alongside an SHT optimization exercise. The analysis was conducted through microstructural characterization, differential scanning calorimetry, and compositional homogeneity measurements, quantifying (i) the dissolution and microstructural evolution of the inter-dendritic constituents, (ii) the shift in thermo-physical characteristics of the material, and (iii) the change in compositional homogeneity across the microstructure, in order to gain further understanding of these phenomena during the progression of the SHT. During the early stages of SHT, the coarse cellular γ′/narrow γ channel inter-dendritic constituents which were the last areas to solidify during casting, progressively dissolve; homogenization between these inter-dendritic areas and adjacent dendritic areas leads to a rapid increase in the incipient melting temperature jats:italicT</jats:italic> jats:subIM</jats:sub>. The fine γ/γ′ morphology which were the first inter-dendritic constituents to solidify after primary γ dendrite solidification were found to progressively coarsen; however, subsequent dissolution of these coarsened γ/γ′ inter-dendritic areas did not result in significant increases in the jats:italicT</jats:italic> jats:subIM</jats:sub> until the near-complete dissolution of these inter-dendritic areas. After the final SHT step, residual compositional micro-segregation could still be detected across the microstructure despite the near-complete dissolution of these remnant inter-dendritic areas; even so the jats:italicT</jats:italic> jats:subIM</jats:sub> of the material approached the solidus temperature of the alloy.</jats:p>