The impact of non-ideal compressible flows on the fluid-dynamic design of axial turbine stages is examined. First, the classical similarity equation is revised and extended to account for the effect of flow non-ideality and compressibility. Then, the influence of the most relevant design parameters is investigated through the application of a dimensionless turbine stage model embedding a first-principles loss model. The results show that the selection of optimal duty coefficients is scarcely affected by the molecular complexity of the working fluid, whereas compressibility effects produce an offset in the efficiency trends and in the optimal flow coefficient. Furthermore, flow non-ideality can lead to either an increase or a decrease of stage efficiency of the order of 2–3% relative to turbines designed to operate in dilute gas state. This effect can be predicted at preliminary design phase through the evaluation of the isentropic pressure-volume exponent. 3D RANS simulations of selected test cases corroborate the trends predicted with the reduced-order turbine stage model.