Nickel-based superalloys have been extensively used in the aerospace industry due to their excellent mechanical properties at elevated temperatures. The mechanical properties of the Inconel-718 majorly depend on its microstructure which can be controlled using thermomechanical treatments. Machining of the heat-treated Inconel-718 component is very difficult due to very high hardness. This paper investigates the relationship between the material microstructure developed through a thermomechanical process and the machinability through micro-drilling of Inconel-718. In this study, a wide range of microstructures with hardness ranging from 179 HV to 461 HV was achieved by different thermomechanical and heat-treatment processes. Flank wear, thrust force, and burr height analysis were carried out to understand the machining behavior after micro-drilling. Electron back scattered diffraction (EBSD) technique was used to characterize the microstructure. No correlation between grain size and thrust force was observed. However, a clear trend between thrust force and hardness was established. It was also observed through misorientation analysis that the machined surface deforms significantly with material hardness.