Investigation, conservation, and exploitation of seas require platforms capable of accomplishing a wide variety of missions in harsh environments with restricted human intervention for long periods of time. Autonomous Underwater Vehicles (AUVs) are excellent tools for carrying out these missions due to their versatility and ability to access remote sites. However, despite the improvement of their capabilities, their development is not devoid of challenges. Endurance, among others, such as underwater communications or autonomy, is still a pending subject. Current battery-based solutions do not offer sufficient endurance and innovative power plants with higher energy content are needed. This work studies the advantages, in terms of endurance, of using a power plant based on Direct Methanol Fuel Cells (DMFCs) to power AUVs. In order to accomplish this, a multi-objective optimization tool that makes use of a genetic algorithm was developed. This tool allows quick preliminary design of AUVs with a DMFC-based power plant, complying with a user-defined payload, operation profile, and restrictions. Six designs based on a real AUV model were studied, and endurance values up to 2 times longer than the corresponding reference AUV were obtained. These results support the benefits of using DMFCs to power AUVs to increase their endurance.