NiTiNOL (Nickel-Titanium) shape memory alloys (SMAs) are ideal replacements for titanium alloys used in bio-medical applications because of their superior properties like shape memory and super elasticity. The machining of NiTiNOL alloy is challenging, as it is a difficult to cut material. Hence, in the current research the experimental studies on machinability aspects of medical grade NiTiNOL SMA during wire electric discharge machining (WEDM) using zinc coated brass wire as electrode material have been carried out. Pulse time (Ton), pause time (Toff), wire feed (WF), and servo voltage (SV) are chosen as varying input process variables and the effects of their combinational values on output responses such as surface roughness (SR), material removal rate (MRR), and tool wear rate (TWR) are studied through response surface methodology (RSM) based developed models. Modified differential evolution (MDE) optimization technique has been developed and the convergence curve of the same has been compared with the results of differential evolution (DE) technique. Scanning electron microscopy (SEM) and energy dispersive X-ray spectrography (EDS) analysis are carried out to study the surface morphology of the machined alloy. SV is found to be more influential process parameter for achieving better MRR with minimal SR and TWR, followed by Ton, Toff, and WF. The WF has good impact on reduced SR and TWR responses and found to be least significant in maximizing MRR.