Fused Filament Fabrication (FFF) is a widely embraced material extrusion (MEX) additive manufacturing (AM) process to produce complex three-dimensional structures, and it is typically used in the fabrication of biodegradable polymers for biomedical applications. However, FFF as a fabrication process for blended polymeric materials needs to be optimized for enhanced mechanical properties. In this work, biodegradable polylactic acid (PLA)/polyhydroxyalkanoate (PHA) dog-bone and notched specimens are printed to determine optimum printing parameters for superior mechanical properties in FFF additive manufacturing. The effect of layer thickness, infill density, and printing bed temperature on mechanical properties is investigated by employing a design of experiments (DoE) approach using response surface methodology (RSM). Experimental results showed the significance of the opted parameters for mechanical properties of the PLA/PHA blend. Then, optimum values for layer thickness, infill density, and printing bed temperature are identified for tensile and impact strength and an empirical relationship between parameters is formulated for low density and cost-effective fabrication. Finally, the analysis of variance (ANOVA) is performed to check the adequacy of the model for the influence of process parameters and their mutual interactions. The verification experiments validated the adequacy of the proposed model for PLA/PHA blend in FFF additive manufacturing.