The application of micro-mechanical cutting operations, such as micro-drilling, is crucial for producing microsystem components. In the production of jet engine parts, Inconel 718 superalloy has been used to produce these components due to its high performance at high temperatures. Due to the low thermal conductivity and the high work hardening tendencies of Inconel 718, a high amount of the cutting temperature dissipates toward the cutting tool instead of the chip. When using micro-scale drilling (micro-drilling), heat dissipation becomes more challenging. This affects the tool life and the machined surface quality; therefore, when machining these alloys, a cutting fluid is required to decrease the high amounts of generated heat. Flood coolant is commonly used to reduce the cutting temperature; however, government regulations have been published for alternative cooling processes to decrease the influences of flood coolant on the environment and the operator’s health. Minimum quantity lubrication (MQL) has been used as an alternative to conventional cutting fluids because it minimizes the consumption of cooling lubricants and reduces the environmental and health impacts; however, pure MQL cooling has an ineffective cooling ability. In order to enhance thermal conductivity, viscosity, and wettability of the MQL base fluid, an MQL-nanofluid was used. This study investigated the performance of a micro-drilling process using an MQL-nanofluid with regard to thrust forces, tool wear, and burr formation, and compared it to flood cooling and a pure MQL. Micro-drilling experiments involving Inconel 718 were conducted using the same cutting parameters, drilling tool, and machining environment for both the MQL and the flood coolant. The results revealed that the MQL-nanofluid approach was promising in terms of machining outputs as well as sustainability.