This paper presents a generalized theoretical model for the optimization of a thermoelectric cooling (TEC) system, in which the thermal conductances from the hot and cold sides of the system are taken into account. Detailed analyses of the optimal allocation of the finite thermal conductance between the cold-side and hot-side heat exchangers of the TEC system are conducted by considering the constraint of the total thermal conductance. The analysis results show that the maximum coefficient of performance (COP) and the maximum cooling capacity of the TEC system can be obtained when the finite total thermal conductance is optimally allocated. Furthermore, the effects of the total thermal conductance and the heat capacity rate of the cooling fluid on the performance of the TEC system and the optimal thermal conductance allocation ratio are also examined. ► A generalized optimization model of a thermoelectric cooling system is developed. ► The model considers the thermal conductances of two sides' heat exchangers. ► Optimization analyses are conducted with a constraint of total thermal conductance. ► Maximum coefficient of performance and cooling capacity can be obtained.