This study provides a comprehensive methodology for optimizing the design of a two-phase micro-channel heat sink. The heat sink parameters are grouped into geometrical parameters, operating parameters, and thermal/fluid parameters. The objective of the proposed methodology is to optimize micro-channel dimensions in pursuit of acceptable values for the thermal/fluid parameters corresponding to a given heat flux, coolant, and overall dimensions of the heat generating device to which the heat sink is attached. The proposed optimization methodology yields an acceptable design region encompassing all possible micro-channel dimensions corresponding to a prescribed coolant flow rate or pressure drop. The designer is left with the decision to select optimum channel dimensions that yield acceptable values of important thermal/fluid parameters that are easily predicted by the optimization procedure.