This paper presents the development of a wrist rehabilitation system with a novel approach for structural design, based on the modeling of an optimization problem solved by a metaheuristic algorithm, Improved Harmony Search (ImHS). It is part of a project for developing low-cost rehabilitation systems expressly designed for the population of Latin American countries. A mixed optimization problem is modeled for the design, where the material type is associated with an integer variable and the dimensions of the components are continuous parameters. The novelty is that each element is calculated individually, but considering the combined effect over the structure. The optimization works simultaneously on both the material selection and the meeting of the associated constraints, to guarantee that the system will not fail because of any load, neither it will be unsafe for the patients, since the operation will always be within the limits considered in the modeling. ImHS is a variant of the Harmony Search algorithm, modified to enhance the exploration and exploitation processes. It is a simple yet powerful metaheuristic, implemented in this development with additional modifications to handle constraints and mixed variables. The proposed approach produced quality results, indicating that ImHS can be applied to solve complex engineering problems, facilitating the manufacture and control processes.