In the coming years, missions to the Moon and Mars shall be the new goals of space flight. The complexity of these missions due to the great distance from Earth and the unforeseen obstacles to settle on another planet have given rise to great concerns for crew health and survival. The need for advanced crew autonomy and a different approach to surgical emergency require new protocols and devices to help future crew medical officers and other crew members in a task of unprecedented difficulty. Hence, the increasing variety of schedules, devices, and protocols being developed. A serious health problem, such as an emerging surgical disease or severe trauma, can jeopardize the mission and survival of the entire crew. Many other difficulties are present in deep-space missions or settlements on other planets, such as communication and supply, also medical, delays, and shortage, and the presence of radiation. Progress in advanced technologies as well as the evolution of robotic surgery and the use of artificial intelligence are other topics of this review. In this particular area of research, even if we are still very far from an “intelligent robot”, this evolution must be evaluated in the light of legislative and ethical considerations. This topic was presented at the annual meeting of the American College of Surgeons—Italy Chapter in 2021.