Remotely operated vehicles (ROVs) provide practical solutions for a wide range of activities in a particularly challenging domain, despite their dependence on support ships and operators. Recent advancements in AI, machine learning, predictive analytics, control theories, and sensor technologies offer opportunities to make ROVs (semi) autonomous in their operations and to remotely test and monitor their dynamics. This study moves towards that goal by formulating a complete navigation, guidance, and control (NGC) system for a six DoF BlueROV2, offering a solution to the current challenges in the field of marine robotics, particularly in the areas of power supply, communication, stability, operational autonomy, localization, and trajectory planning. The vehicle can operate (semi) autonomously, relying on a sensor acoustic USBL localization system, tethered communication with the surface vessel for power, and a line of sight (LOS) guidance system. This strategy transforms the path control problem into a heading control problem, aligning the vehicle’s movement with a dynamically calculated reference point along the desired path. The control system uses PID controllers implemented in the navigator flight controller board. Additionally, an infrastructure has been developed that synchronizes and communicates between the real ROV and its digital twin within the Unity environment. The digital twin acts as a visual representation of the ROV’s movements and considers hydrodynamic behaviors. This approach combines the physical properties of the ROV with the advanced simulation and analysis capabilities of its digital counterpart. All findings were validated at the Point Rouge port located in Marseille and at the port of Ancona. The NGC implemented has proven positive vehicle stability and trajectory tracking in time despite external interferences. Additionally, the digital part has proven to be a reliable infrastructure for a future bidirectional communication system.