Seeking for an available thermal runaway solution is becoming one important and challenging issue in current nanometer ICs. Thermoelectric coolers (TECs) may give a solution. In this paper, a simplified power model of circuits closely associated with temperature with and without repeaters is derived. Based on the surface temperature difference and heat-flow density, an equivalent thermal resistance model for powered TECs is proposed. According to the thermal profile model, the steady-state temperature is calculated for the same chip with two different package forms. Finally, optimizations of p-n couples are performed with the purpose of obtaining the maximum coefficient of performance (COP) and minimum TECs power. As compared with the traditional flip-flop controlled-collapse-chip-connection package, the results reveal desirable conclusions that a 15.8% decrease of the chip stability temperature with the COP optimization at I = 2.5 A and 11.4% steady-state power savings with the 13.2 W TEC power consumption are obtained in a 50-nm technology node. Analysis demonstrates that the maximum COP and minimum power consumed by TECs can be obtained at different optimum numbers of p-n couples, which is independent of electrical current across by TECs.