A three-dimensional integrated circuit having a dual or multiple power domain is capable of less energy consumption operation under a given clock rate, which results in an enhanced power-performance-area (PPA) envelope. Sequential logic operates under a system clock that determines the system throughput, whereas combinational logic operates in a different power domain to control overall system power including dynamic and static power. The sequential logic and clock network may be implemented in one tier of the three-dimensional integrated circuit supplied with a relatively high power supply voltage, whereas the combinational logic may be implemented in another tier of the three-dimensional integrated circuit supplied with a relatively low power supply voltage. Further pipeline reorganization may be implemented to leverage the system energy consumption and performance to an optimal point.