An effective method for performing the thermal optimization of stationary and rotating multichip module (MCM) disks with an unconfined round-jet impingement under space limitation constraint has been successfully developed. The design variables of stationary and rotating MCM disks with an unconfined round-jet impingement include the ratio of jet separation distance to nozzle diameter, Grashof number, jet Reynolds number, and rotational Reynolds number. The total experimental cases for stationary and rotating MCM disks are statistically designed by the central composite design method. In addition, a sensitivity analysis, the so-called analysis of variance, for the design factors has been performed. Among the influencing parameters, the jet Reynolds number dominates the thermal performance, while the Grashof number is found to have the least effect on heat-transfer performance for both stationary and rotating cases. Furthermore, the comparisons between the predictions by using the quadratic response surface methodology and the experimental data for both stationary and rotating cases are made with a satisfactory agreement. Finally, with the sequential quadratic programming technique, a series of thermal optimizations under multiconstraints—such as space, jet Reynolds number, rotational Reynolds number, nozzle exit velocity, disk rotational speed, and various power consumptions—has been systematically explored and discussed.