PREMIERE will integrate challenges identified by the EPSRC Prosperity Outcomes and the Industrial Strategy Challenge Fund (ISCF) in healthcare (Healthy Nation), energy (Resilient Nation), manufacturing and digital technologies (Resilient Nation, Productive Nation) as areas to drive economic growth. The programme will bring together a multi-disciplinary team of researchers to create unprecedented impact in these sectors through the creation of a next-generation predictive framework for complex multiphase systems. Importantly, the framework methodology will span purely physics-driven, CFD-mediated solutions at one extreme, and data-centric solutions at the other where the complexity of the phenomena masks the underlying physics. The framework will advance the current state-of-the-art in uncertainty quantification, adjoint sensitivity, data-assimilation, ensemble methods, CFD, and design of experiments to 'blend' the two extremes in order to create ultra-fast multi-fidelity, predictive models, supported by cutting-edge experimental investigations. This transformative technology will be sufficiently generic so as to address a wide spectrum of challenges across the ISCF areas, and will empower the user with optimal compromises between off-line (modelling) and on-line (simulation) efforts so as to meet an a priori 'error bar' on the model outputs. The investigators' synergy, and their long-standing industrial collaborations, will ensure that PREMIERE will result in a paradigm-shift in multiphase flow research worldwide. We will demonstrate our capabilities using exemplar challenges, of central importance to their respective sectors in close collaboration with our industrial and healthcare partners. Our PREMIERE framework will provide novel and more efficient manufacturing processes, reliable design tools for the oil-and-gas industry, which remove conservatism in design, improve safety management, and reduce emissions and carbon footprint. This framework will also provide enabling technology for the design, operation, and optimisation of the next-generation nuclear reactors, and associated reprocessing, as well as patient-specific therapies for diseases such as acute compartment syndrome.