Arguably one of the most important factors in the fast deployment of advanced nuclear reactors, with major improvements in safety, is the development and qualification of radiation and corrosion tolerant materials, that serve as the structural components in reactor cores. However, the discovery, improvement, and assessment of materials resistant to radiation and corrosion in the advanced reactors’ extreme environments is quite demanding, time-consuming, and costly, which represents a significant barrier to materials innovation and qualification for nuclear energy. This short review highlights a novel, integrated, high-throughput (HTP) research framework to develop understanding and predictive models for irradiation at high doses and molten salt corrosion responses of structural Compositionally Complex Alloys (CCAs), with the objective to accelerate materials discovery for high-temperature nuclear structural applications. Using a novel in situ alloying technique, arrays of additively manufactured bulk CCAs are processed, heat-treated, and characterized, while still attached to the build plate. Leveraging recent development in automation of heavy-ion irradiation experiments at the University of Wisconsin Ion Beam Laboratory, arrays of CCAs can be rapidly irradiated to hundreds of dpa up to 800 °C. An innovative droplet corrosion method is also used to test molten salt corrosion behavior of CCAs arrays. Automated and rapid characterization methods are used to assess the irradiation and molten salt corrosion resistance of CCAs. Finally, a brief discussion of the results is presented considering future use of machine-learning-based methods to develop useful trends and highlight features of importance. Using this novel HTP approach, a robust and reliable database containing literally hundreds of data points for irradiation and corrosion responses of CCAs can be established within a year, which is considered a significant increase in the pace of nuclear structural materials research and discovery.