Indiana University-Purdue University Indianapolis (IUPUI) / Plastic injection molding is a versatile process and a major part of the present plastic manufacturing industry. Traditional die design is limited to straight (drilled) cooling channels, which dont impart optimal thermal (or thermos-mechanical) per- formance. Moreover, reducing the cycle time in plastic injection molding has become significantly important to the industry nowadays. One approach that has been pro- posed is to use conformal cooling channels. With the advent of additive manufacturing technology, injection molding tools with conformal cooling channels are now possible. However, optimum conformal channels based on thermo-mechanical performance are not found. This study proposes a design methodology to generate optimized design configurations of such channels in plastic injection molds. Numerical models have been developed here to represent the thermo-mechanical behavior of the molds and predict the stress and cooling time. The model is then validated experimentally and used in conjunction with DOE (Design of Experiments) to study the effect of differ- ent design parameters of the channels on the die performance. Design of experiments (DOEs) is used to study the effect of critical design parameters of conformal channels as well as their cross section geometries. These DOEs are conducted to identify op- timal designs of conformal cooling channels which can be incorporated into injection molds that are used to manufacture cylindrical and conical shapes of plastic parts. Though these are simplified forms, the study provides useful insight into the poten- tial deign parameters for all kind of injection molds.Based on the DOEs, designs for best thermo-mechanical performance are identified (referred to as ”optimum”). The optimization study is basically a trade-off and the solution is based on a specific sample size. This approach is highly result-oriented and provides guidelines for selecting optimum design solutions given the plastic part thickness.