Renewable integration into the electricity system of Great Britain (GB) is causing considerable demand for additional flexibility from plants. In particular, a considerable share of this flexibility may be dispatched to secure post-fault transient frequency dynamics. Pursuant to the unprecedented changes to the traditional portfolio of generation sources, this work presents a detailed analysis of the potential system-level value of unlocking flexibility from nuclear electricity production. A rigorous enhanced mixed integer linear programming (MILP) unit commitment formulation is adopted to simulate several generation-demand scenarios where different layers of flexibility are associated to the operation of nuclear power plants. Moreover, the proposed optimisation model is able to assess the benefit of the large contribution to the system inertial response provided by nuclear power plants. This is made possible by considering a set of linearised inertia-dependent and multi-speed constraints on post fault frequency dynamics. Several case studies are introduced considering 2050 GB low-carbon scenarios. The value of operating the nuclear fleet under more flexible paradigms is assessed, including environmental considerations quantified in terms of system-level CO2 emissions’ reduction.