Nickel-based superalloy Inc-718 has become an indispensable alloy in critical sectors, especially in the aerospace industry, thanks to its unique characteristics. However, some properties of the alloy (especially low thermal conductivity and hot hardness) cause difficulties in its machinability. For this reason, comprehensive studies to improve the machinability of Inc-718 alloy by considering the microstructural properties are guiding. In this context, the present study uses various methods to increase the machinability efficiency of Inc-718, while also investigating their effect on microstructural properties. Firstly, the effect of the pre-heating process (hot), pure-MQL (PMQL), nanofluid-MQL (NMQL), and hybrid methods (hot+PMQL and hot-NMQL) on the surface roughness, cutting forces, tool wear, vibration, and temperature was investigated while milling Inc-718 surfaces. Then the utilization of Electron Backscatter Diffraction (EBSD) facilitated a comprehensive examination of microstructural behavior, with a specific focus on Euler-colored maps and phase distribution maps, providing valuable insights into the material's behavior under distinct milling conditions. As a result, hot+PMQL, hot+SiC-NMQL, and hot+Al2O3-NMQL provided an important contribution to the improvement of machinability characteristics. Also, it was seen that in EBSD analysis, a limited area is affected by heat in the hot machining environment. The crystal orientations of the pre-heated and hybrid machined Inc-718 alloy are highly similar to that of the dry-machined alloy. This similarity indicates that the removal of the heated layer from the workpiece during the milling process contributes to the preservation of the microstructure.