A three-dimensional solid-fluid conjugated model is used to investigate and optimize the performances of two-, three-, and four-layered microchannel heat sinks. In the optimization process, constraints of fixed total pumping power and fixed total channel height are adopted, and the thermal resistance and bottom wall temperature uniformity are taken as the objective functions. The flow configuration, channel height, and pumping power in each layer are optimized. The results show that more uniform temperature distribution and lower thermal resistance occur at flow configuration (0, 1) for the two-layered microchannel heat sink, (0, 1, 1) for the three-layered microchannel heat sink, and (0, 1, 1, 1) for the four-layered microchannel heat sink. The channel height and pumping power in the bottom layer are dominant over those in the other layers. The optimal design requires a smaller bottom channel height and a higher pumping power than the average value in each layer. The multilayered microchannel heat sink with more layer numbers can achieve a more uniform bottom wall temperature and can also lead to a reduction in the thermal resistance.