The STEP environment will include magnetic, thermal, mechanical and environmental loads far greater than those seen in the Joint European Torus campaigns of the past decade or currently contemplated for ITER. Greater still are the neutron peak dose rates of 10^-6displacements per atom, per second, which in-vessel materials in STEP are anticipated to be exposed to. Reduced activation and high-fluence resilience therefore dominate the materials strategy to support the STEP Programme. The latter covers the full life cycle from down selected compositions and new microstructural developments to irradiation-informed modelling and end of life strategies. This paper discusses how the materials downselection is oriented in plant power trade-off space, outline development of an advanced ferritic-martensitic structural steel, describes the ‘Design by Fundamentals’ mesoscale modelling approach and reports on some of the waste mitigation routes intended to make STEP operations as sustainable as possible.