Biocompatibility is usually observed as the absence of communication of a material with living tissue. Commercially pure titanium grade-2 has become the preferred biocompatible material for various devices mainly used in orthopedic and dental implants and it is also used in aviation and aircraft. Commercially pure titanium has good ductility, higher stiffness, and fatigue resistance. The novelty of the present research work was focused on studying the effect of wire electric discharge machining factors on surface roughness, material removal rate, crack density, and white layer thickness. After machining, the wire electro-discharge machined surface was analyzed through a scanning electron microscope. Further energy dispersive analysis and X-ray diffraction spectroscopy techniques were applied to investigate the material migration on a work surface and brass wire. Each output response has been modeled through analysis of variance to analyze the adequacy. It was observed that pulse on time, pulse off time, peak current, and spark gap voltage are the most significant factors. These factors have been significantly deteriorating the microstructure of machined samples remarkably deeper, leading to wider craters, globules of debris, and micro-cracks. A white layer thickness was also observed in a discontinuous and non-uniform pattern at the cross-section of the machined sample due to rapid heating and quenching phenomena in the wire electric discharge machining process. A multi-objective optimization “desirability” function was applied to obtain the optimal solutions by numerical and graphical methods. In essence, the wire electric discharge machining is a non-traditional process to achieve the accuracy of biocompatibility parts of commercially pure titanium and also finds the improvement in surface morphology.