This article presents the optimization of two-stage thermoelectric (TE) coolers arranged in two practical design configurations, and the optimization methods can be extended to other multi-stage designs. The first arrangement is the conventional pyramid-styled multi-stage TE cooler, in which the supplied electric current is uni-directional with the top stage of the unit being the coldest. A second design configuration comprises the cuboid-styled multi-stage cooler, in which the supplied current can be alternated, and thus, the top and bottom stages can be switched between heating and cooling modes. Optimizations for the two-stage TE coolers are performed at both its two optima, namely, the point of maximum cooling capacity and optimal coefficient of performance, or COP for short. In the first design of the TE cooler, the optimization goal is geared towards determining the optimum ratio of the number of TE modules between stages when the total number of modules is kept constant, while in the second design configuration, it is to solve for the optimum ratio of electric current between stages. Optimum design parameters for the two types of two-stage TE coolers are compared on given conditions. For practical purposes, all properties of TEs are based on commercial TE materials.