Inconel 625, nickel based alloy, is found in gas turbine blades, seals, rings, shafts, and turbine disks. On the other hand, the manufacturing of this alloy is challenging, mainly when machining processes are used due to excellent mechanical properties. Application of nanofluids in minimum quantity lubrication (MQL) shows gaining importance in the machining process, which is economical and eco-friendly. The principal objective of this investigational work is to study the influence of three types of nanofluids in the MQL turning of Inconel 625 nickel based alloys. The used nanofluids are multi-walled carbon nanotubes (CNT), alumina (Al2O3) and copper oxide (CUO) dispersed in vegetable oil. Taguchi-based L27 orthogonal array is used for the experimental design. The parameter optimization of design variables over response is carried out by the use of Taguchi-based derringer's desirability function. The design variables are machining parameters (speed, feed), nanofluids (Al2O3, CNT, CUO), and three different weight percentage (0.1, 0.25, and 0.5 wt. %). The results showed that minimum values of surface roughness could be achieved at 0.10 wt. % of nanoparticles, CNT nanofluids, a cutting speed of 40 m/min and a feed rate of 0.17 mm/rev. In the interim, minimal tool wear can be achieved by the application of 0.50 wt% nanoparticle concentration, Al2O3 nanofluids, 40 m/min speed and 0.14 mm/rev feed rate. Further statistical analysis emphasized that cutting velocity and nanofluids have a significant effect on Ra and Vba. Abrasion and small adhesion are the dominant wear types. Desirability analysis revealed 0.5 wt.%, Al2O3 nanofluids, 40 m/min and 0.20 mm/rev are found as optimized parameter levels which simultaneously optimize the surface roughness and flank wear. At the optimized cutting conditions, Al2O3 nanofluids exhibit the improvement of Ra and Vba by 9.0% 4.26%, and 5.4%, 65% as compared to CNT and CUO nanofluids. Thus the Al2O3 nanofluids show the overall performance on machinability characteristics that of CNT and CUO nanofluids. This finding is a step towards sustainable machining of difficult-to-process material such as nickel based alloy. © 2019 SAE International. All Rights Reserved.