Detailed statistical trend analysis of thermoplastic elastomers based on poly (phenylene ether) (PPE), polystyrene (PS), ethylene vinyl acetate (EVA) and styrene-ethylene-butylene-styrene (SEBS) was done through Design Expert software by Stat-Ease. D optimal crossed design was followed to capture the interaction with the parameters. Effect of blend ratio, vinyl acetate (VA) content of EVA, molecular weight (MW) of SEBS and intrinsic viscosity (IV) of PPE on the blend performance (response) was studied in detail. Design of Experiment (DOE) analysis showed the "optimized formulation" of the blend. Increase in PPE-polystyrene (PS) content increased tensile strength and modulus of the blend, followed by a decrease in strain at break. However, EVA had a reverse effect on tensile strength and modulus. Strain at break increased significantly with increasing SEBS content in the blend. Graphical and numerical optimization showed that superior mechanical properties (tensile strength, strain at break and modulus) could be achieved at VA content - 50% at a particular loading of EVA. Low MW SEBS was found to be more compatible with the other components of the blend. Mechanical properties of the quaternary blend were marginally affected with change in IV of PPE in the range of 0.33 to 0.46