For the cooling system of plastic injection mold affects significantly the productivity and quality of the finial products, the cooling system design is of great importance. In this paper, considering the location, size, number of cooling channels and mold material properties, the optimization design of heterogeneous injection mold cooling system is discussed to achieve simultaneously fast and uniform cooling. A mathematical model is constructed in which the part temperature distribution uniformity and production efficiency are taken as the objective function for cooling system design of heterogeneous injection mold. For the reason of the non-linearity of design problem and the coupling of geometric with material variable, the design problem is divided into two sub-problems and the combining algorithm is used in such way that, the geometric optimization sub-problem is solved by Hooke-Jeeves method and the material optimization sub-problem is solved by particle swarm optimization (PSO) method. The effectiveness of the approach is illustrated by a design example of injection mold cooling system.