Incorporating specified safety and production targets during the design phase of an engineered facility can effectively support reductions in construction and operation costs of nuclear power plants. In addition, this supports efforts toward making nuclear power technology more competitive and profitable than other electric power production forms by incorporating operational and design features into the design phase that directly support the increased likelihood of meeting such originating targets. Unavailability is the key parameter to establish plant-level capabilities that cascade down to function, system, and component levels to ensure that all sources of unavailability are addressed in the facility's design phases. In this article, two methods are presented to propose unavailability targets for nuclear reactor systems to risk-inform and optimize the design features, from an availability perspective: the first method is a simple method, and the second is a non-dominated sorting genetic algorithm III (NSGA-III) multi-objective optimization. These iterative methods are demonstrated in this paper for a hypothetical facility with a design maturity such that there is knowing the main components to comply with the engineering and security functions of the systems. With an assumed mature design, it is implied that generic data to execute quantitative reliability, and availability analyses are available at the systems levels that are sufficient to support a design-specific probabilistic risk assessment (PRA). The proposed methods modify the probabilities of basic events within the fault tree structures that model system and component unavailability sources that will be required for the facility’s operating license. The methods provided are applied to visualize the characteristics of the problem and the quantitative results. This work forms the basis for future work in which design alternatives affecting unavailabilities can be estimated and compared to their associated unavailability targets at different levels of granularity.