This paper presents a methodology to design optimal water reclamation systems for long-duration space missions. These systems employ, separately, numerous technologies and are required to satisfy multiple goals. However, each of the available technologies may not meet these goals by itself. Instead, it is proposed to evaluate the optimal design of such systems employing, simultaneously, several technologies. First, mathematical models for each technology considered are developed. These models are employed to optimize two of these technologies, demonstrating that significant “cost” reductions are possible. Finally, hybrid systems with multiple technologies are designed and optimized to meet multiple objectives. The obtained results show that these systems outperform single technology based water reclamation systems.