Thermoelectric coolers are often used as reliable energy converters in a large range of applications. For design considerations, it is crucial to establish an effective methodology to determine and optimize the TEC performance within the cooling system constraints. For this purpose, firstly, three approaches are used to obtain the internal parameters of a given thermoelectric module. For these three estimating procedures, the simulated pumping powers are in the sequence of method III < method II < method I for each temperature difference. Hence, good precision of the simulated data are obtained by averaging the results of these three methods. Then, design optimizations of a thermoelectric assembly are conducted to obtain the device parameter, efficiency, and maximum power, respectively. Results show it is simple and effective way for design of a thermoelectric cooling system.