The great impact of the injection molding cooling process on both productivity and product quality makes it essential to optimize the cooling conditions as well as the cooling system design. The current practice in injection molding process development, to identify the final operating conditions, which is a time consuming iteration between model design and product line, is costly in both material and time. This defect in the process development also raises the necessity to establish a method, which can provide the manufacturer not only with an optimum but also with a window around the optimum for the operating conditions, so as to avoid this time with consuming process to determine the feasible operating conditions. This paper presents a methodology, which combines an optimization algorithm with a mold cooling analysis, to obtain an optimal cooling processing condition and a cooling window in the injection molding of plastics as an aid for mold designing and manufacturing. The cooling effect, which is characterized through uniform cooling and short cooling time, is quantified in terms of mold cooling simulation output. A mathematical model is then formulated based on semi-empirical criteria and solved numerically by implementing an optimization algorithm. Based upon the resultant final optimum cooling condition, a relaxation scheme scheme is developed by the authors and performed, followed by a sensitivity analysis to determine the cooling window. At last, the application of this method is demonstrated by two industrial molds: a drilling housing and a compact drill battery pack. This approach will help in designing a proper cooling system for a mold and in determining an operating range to achieve better part quality and higher productivity.