Thermoelectric cooler employs Peltier effect for dissipating heat in an electronic casing structure. It shows exceptional rewards over conservative cooling skill via quiet process, extended life span, and effortless integration. Nevertheless, Joule heating results in the accumulation of internal heat thereby exposes thermoelectric cooler towards the risk of thermo-mechanical breakdown all through continuous operations in pragmatic thermal surroundings. A relative analysis of the effect of thickness size on thermal stress on MoSi2 and Mo5SiB2 by the COMSOL-Multiphysics platform is offered. Mo5SiB2 in comparison to MoSi2 has lower anisotropic single crystal elastic moduli, along with lower shear modulus. Mo5SiB2 has a slightly higher bulk, shear and Young’s than MoSi2. RT Vickers hardness of Mo5SiB2 is much larger than those of MoSi2. Fracture toughness is comparable to those of MoSi2. In this paper, a 3D module of thermoelectric materials MoSi2 and Mo5SiB2 is designed on the way to examine the effect of thermal stress with increasing thickness of the material taking into consideration the temperature reliant TE material traits. One side of the module is kept at 300K with fixed constraints while the other side is kept at 1200K. It has been observed that the thermal stress induced in MoSi2 and Mo5SiB2 decrease exponentially with increase in thickness of the material. Beyond thickness of 500 nm, the incremental difference in thermal stress is not large although a slight rise in stress level is observed at thickness 700 nm. It was found that the induced thermal stress for a particular thickness in Mo5SiB2 is lower than MoSi2. For MoSi2, the voltage swings across the length is from -2.42mV to 1.09 mV whereas for Mo5SiB2, the voltage swings across the length is from -1.87 mV to 1.64 mV. It was found that excessive elevated levels of thermal strain may source the dislocations as well as cracks in the layers of the material.