In recent times, nickel-based super alloys are widely utilized in aviation, processing, and marine industries owing to their supreme ability to retain the mechanical properties at elevated temperature in combination with remarkable resistance to corrosion. Some of the properties of these alloys such as low thermal conductivity, strain hardening tendency, chemical affinity, and presence of hard and abrasives phases in the microstructure render these materials very difficult-to-cut using conventional machining processes. In this work, an experimental setup was developed and integrated with the existing electrical discharge machining system for carrying out powder-mixed electrical discharge machining process for Inconel 625. The experiments were planned and conducted by varying five different variables, that is, powder concentration, peak current, pulse-on time, duty cycle, and gap voltage based on the central composite design of response surface methodology. Effects of these parameters along with powder concentration were investigated on various surface integrity aspects including surface morphology, surface roughness, surface microhardness, change in the composition of the machined surface, and residual stress. Results clearly indicated that addition of powder to dielectric has significantly improved surface integrity compared to pure dielectric. Among the powders used, silicon has resulted in highest microhardness, that is, almost 14% more than graphite. Lowest surface roughness (approximately 50% less than pure kerosene) and least residual stress were obtained using silicon powder (approximately 8% less than graphite-mixed dielectric). Relative content of nickel was reduced at the expense of Nb and Mo after addition of powders like aluminum and graphite in dielectric during electrical discharge machining.