The optimization of process parameters such as applied voltage, orifice diameter, solvent system, and solvent ratio for electrospinning of neat polymers, polylactic acid (PLA) and poly (& x454;-caprolactone) (PCL), to obtain uniform, randomly oriented nanofibers with minimum diameter variation and beaded structures has been critically discussed. The paper focuses on establishing a sequential optimization technique for arriving at a common set of electrospinning process parameters for individual polymers, such as, applied voltages, orifice diameters, solvent mixtures, solvent ratios, to be used in the fabrication of electrospun nanofibrous mats (ENMs) of blended polymers. In this study, the effect of variation of applied voltages, orifice diameters, solvent mixtures, solvent ratios, PLA/PCL blending ratios, solution concentration of blends and flow rate were reported via morphological analysis of electrospun nanofibers. The set of optimal process parameters obtained for both PLA and PCL were adopted for the fabrication of ENMs based on the PLA/PCL blends. The paper further deliberates on the physical performance of PLA/PCL based ENMs in acidic, basic and neutral release media. Thus, the study establishes a hierarchical processing optimization route for designing blended ENMs by following a set of variable electrospinning process parameters.