The development of autonomous greenhouses has caught the interest of many researchers and industrial considering their potential of offering an optimal environment for the growth of high-quality crops with minimum resources. Since an autonomous greenhouse is a mechatronic system, the consideration of its subsystem (e.g. heating systems) and component (e.g. actuators and sensors) interactions early in the design phase can ease the product development process. Indeed, this consideration could shorten the design process, reduce the number of redesign loops, and improve the performance of the overall mechatronic system. In the case of a greenhouse, it would lead to a higher quality of the crops and a better management of resources. In this work, the layout design of a general autonomous greenhouse is translated into an optimization problem statement while considering product-related dependencies. Then, a genetic algorithm is used to carry out the optimization of the layout design. The methodology is applied to the design of a fully autonomous greenhouse (45 cm × 30 cm × 30 cm) for the growth of plants in space. Although some objectives are conflictual, the developed algorithm proposes a compromise to obtain a near-optimal feasible layout design. The algorithm was also able to optimize the volume of components (occupied space) while considering the energy consumption and the overall mass. Their respective summed values are 2844.32 cm3, which represents 7% of the total volume, 5.86 W, and 655.8 g.