Nuclear technologies have the potential to play a major role in the transition to a global net-zero society. Their primary advantage is the capability to deliver controllable 24/7 energy on demand. However, as a prerequisite for successful worldwide application, significant innovation will be required to create the nuclear systems of the 21st century, the need of the hour. The pros (low harmful emissions, high reliability, low operational expenses, and high energy density) and cons (environmental damage, fuel waste disposal concerns, limited uranium reserves, and long construction time-frame) of nuclear are discussed and analysed at different levels—the societal and public recognition and concerns (accidents, weapons, mining, and waste) as well as the scientific/engineering and economic level—to assure a demand-driven development. Based on the analysis of the different challenges, a vision for the nuclear system of the 21st century is synthesised consisting of three pillars—unlimited nuclear energy, zero waste nuclear, and accident-free nuclear. These three combined visions are then transformed into dedicated and verifiable missions that are discussed, in detail, regarding challenges and opportunities. In the following, a stepwise approach to the development of such a highly innovative nuclear system is described. Essential steps to assure active risk reduction and the delivery of quick progress are derived as answers to the critique on the currently observed extensive construction time and cost overruns on new nuclear plants. The 4-step process consisting of basic studies, experimental zero power reactor, small-scale demonstrator, and industrial demonstrator is described. The four steps, including sub-steps, deliver the pathway to a successful implementation of such a ground-breaking new nuclear system. The potential sub-steps are discussed with the view not only of the scientific development challenges but also as an approach to reduce the regulatory challenges of a novel nuclear technology.