This paper proposes an integrated design and optimization approach for radial inflow turbines consisting of an automated preliminary design module and a flexible three-dimensional multidisciplinary optimization module. The latter was constructed by an evolution algorithm, a genetic algorithm-assisted self-learning artificial neural network and a dynamic sampling database. The 3-D multidisciplinary optimization approach was validated by the original T-100 turbine and the T-100re turbine obtained from the automated preliminary design approach, for maximizing the total-to-static efficiency and minimizing the rotor weight while keeping the mass flow rate constant and stress limitation satisfied. The validation results indicate that the total-to-static efficiency is 89.6%, increased by 1.3%, and the rotor weight is reduced by 0.14 kg (14.6%) based on the T-100re turbine, while the efficiency is 88.2%, increased by 2.2% and the weight is reduced by 0.49 kg (37.4%) based on the original T-100 turbine. Moreover, the T-100re turbine shows better performance at the preliminary design stage and conserves this advantage to the end, though both the aerodynamic performance of the T-100 and the T-100re turbine are improved after 3-D optimization. At the same time, it is implied that the preliminary design plays an essential role in the radial inflow turbine design process, and it is hard for only 3-D optimization to get a further performance improvement.