Any severe motor disability is a condition that limits the ability to interact with the environment, even the domestic one, caused by the loss of control over one’s mobility. This work presents RoboEYE, a power wheelchair designed to allow users to move easily and autonomously within their homes. To achieve this goal, an innovative, cost-effective and user-friendly control system was designed, in which a non-invasive eye tracker, a monitor, and a 3D camera represent some of the core elements. RoboEYE integrates functionalities from the mobile robotics field into a standard power wheelchair, with the main advantage of providing the user with two driving options and comfortable navigation. The most intuitive and direct modality foresees the continuous control of frontal and angular wheelchair velocities by gazing at different areas of the monitor. The second, semi-autonomous modality allows navigation toward a selected point in the environment by just pointing and activating the wished destination while the system autonomously plans and follows the trajectory that brings the wheelchair to that point. The purpose of this work was to develop the control structure and driving interface designs of the aforementioned driving modalities taking into account also uncertainties in gaze detection and other sources of uncertainty related to the components to ensure user safety. Furthermore, the driving modalities, in particular the semi-autonomous one, were modeled and qualified through numerical simulations and experimental verification by testing volunteers, who are regular users of standard electric wheelchairs, to verify the efficiency, reliability and safety of the proposed system for domestic use. RoboEYE resulted suitable for environments with narrow passages wider than 1 m, which is comparable with a standard domestic door and due to its properties with large commercialization potential.