This paper provides the formulation and description of the framework and methodology for a Durability Assessment-based Design approach for structures made of the Ultra-High-Durability Concrete materials conceived, produced and investigated in the project ReSHEALience (Rethinking coastal defence and Green-energy Service infrastructures through enHancEd-durAbiLity high-performance cement-based materials) funded by the European Commission within the Horizon 2020 Research and Innovation programme (Call NMBP 2016–2017 topic 06-2017 GA 780624). The project consortium, coordinated by Politecnico di Milano, gathers 13 partners from 7 countries, including 6 academic institutions and 7 industrial partners, covering the whole value chain of the concrete construction industry. The innovative design concept informing the whole approach herein presented has been formulated shifting from a set of prescriptions, mainly referring to material composition and also including, in case, an allowable level of damage defined and quantified in order not to compromise the intended level of “passive” protection of sensitive material and structural parts (deemed-to-satisfy approach; avoidance-of-deterioration approach), to the prediction of the evolution of the serviceability and ultimate limit state performance indicators, as relevant to the application, as a function of scenario-based aging and degradation mechanisms. The new material and design concepts developed in the project are being validated through design, construction and long-term monitoring in six full-scale proofs-of concept, selected as representative of cutting edge economy sectors, such as green energy, Blue Growth and conservation of R/C heritage. As a case study example, in this paper, the approach is applied to a basin for collecting water from a geothermal power plant which has been built using tailored Ultra-High-Durability Concrete (UHDC) mixtures and implementing an innovative precast slab-and-buttress structural concept in order to significantly reduce the thickness of the basin walls. The geothermal water contains a high amount of sulphates and chlorides, hence acting both as static load and chemical aggressive. The main focus of the analysis, and the main novelty of the proposed approach is the prediction of the long-term performance of UHDC structures, combining classical structural design methodologies, including, e.g., cross-section and yield line design approaches, with material degradation laws calibrated through tailored tests. This will allow us to anticipate the evolution of the structural performance, as a function of exposure time to the aggressive environment, which will be validated against continuous monitoring, and pave the way towards a holistic design approach. This moves from the material to the structural durability level, anticipating the evolution of the structural performance and quantifying the remarkable resulting increase in the service life of structures made of UHDC, as compared to companion analogous ones made with ordinary reinforced concrete solutions.