As demand for mobility and energy grows, so does the need to cut carbon emissions – driving the search for eco-efficient, customisable concretes that ensure long-term performance. However, knowledge from traditional Portland-clinker systems cannot be directly applied to these innovative materials, which involve complex chemical and mechanical interactions. Unlike metals, the fatigue degradation of concrete is still poorly understood. The ERC-funded FATRESCON project aims to create a pioneering methodology to link the chemical and microstructural makeup of novel concretes to their fatigue resistance. By integrating advanced modelling, multiscale mechanics, machine learning and experimental validation, FATRESCON will provide the scientific tools needed to design and implement eco-efficient concrete in sustainable, long-lasting infrastructure.