This study investigates the performance of biocompatible polylactic acid (PLA) processed through material extrusion/fused filament fabrication (FFF). In this study, the significant FFF input parameters, such as layer deposition, infill angle (degree), and infill percentage (%), were designated to process the PLA based on the screening design experiments. Following Box–Behnken design (BBD), the different input conditions were analyzed to evaluate the performance by assessing the characteristics such as ultimate tensile strength (UTS) and relative density (RD). Printing speed (30 mm/s), nozzle temperature (200°C), and bed temperature (70°C) are considered as fixed input parameters. The novel combination of BBD approach with the Complex Proportional Assessment (COPRAS) technique was employed to obtain the appropriate input conditions. It was beneficial to attain the individual parameter's contribution to the PLA characteristics through analysis of variance and best alternative condition through degree of utility. The combined approach was validated with a composite desirability index “D.” Finally, the hybrid approach yielded better results, such as a maximum ultimate tensile strength (UTS) of 37.43 MPa, relative density (RD) 99.12%, and microhardness 52 HRB under the layer deposition: 0.12 mm, infill angle: 0°, and infill percentage: 100% in the printed biocompatible PLA.