The present experimental study aims to scrutinize the effect of different process parameters on the material removal rate (MRR) and surface roughness (SR) of titanium grade 12 alloy during wire electro-discharge machining (WEDM) using response surface methodology. Four parameters (pulse-on time, pulse-off time, wire feed and gap voltage) and three levels of each selected variable are considered to conduct the experimental work. Depending on experimental results, a mathematical model is generated for both MRR and SR. An analysis of variance (Anova) study is performed to find significant process parameters. The Anova results show that the developed models for both MRR and SR are significant, and pulse-on time is found to be the most significant parameter. Additionally, the desirability approach is used to scrutinize the single-objective and multi-objective criteria of response variables. The desirability functions for all of the cases are found to be 1. The maximum MRR is observed to be 12.4845 mm3/s, while the minimum value of SR is found to be 1.4911 μm. For multi-objective optimization, the maximum value of MRR and the minimum value of SR are obtained as 12.0942 mm3/min and 1.7167 μm, respectively. Finally, the surface morphology of the machined surfaces is examined using scanning electron microscopy micrographs.