Any material used in a nuclear reactor facility must go through an extensive review and qualification, involving many tests and analyses. In late 2019, Alloy 617 was added to the American Society of Mechanical Engineers (ASME) code, representing the first hightemperature material cleared for commercial nuclear reactor use in the United States. since the 1990s. Without new materials, the promise of advanced fission and fusion reactor designs will not be realized (Allen et al., 2010). Similarly, the need to improve current designs and reactor components to extend reactor lifetimes may require deeper understanding of the behavior of nuclear materials under extreme conditions (Was et al., 2019). Advanced reactor concepts will require the materials and components to be resistant to 1) higher temperatures than experienced with current light water reactors, 2) corrosion with liquid salts and liquid metals, and 3) high radiation fields (neutron, ion, and gamma/beta radiation fields). Materials that need to be licensed for use in the nuclear fuel cycle from reactor operation to long-term geologic disposal undergo unparalleled scrutiny. How can this process be sped up without jeopardizing future operational safety? Modern computational predictive tools could help to accelerate development and qualification of advanced materials (Devanathan et al., 2010). However, this may not necessarily negate the requirement for extensive long-term testing of material properties to satisfy regulatory requirements. In this article, as well as discussing the role of ion irradiation studies for nuclear materials research, the potential opportunities for in-situ liquid/gas cell electron microscopy (LC-EM) and Cryo-Electron Microscopy (CryoEM) will be discussed.Ion irradiation in the transmission electron microscope (TEM) has been an important method for testing radiation damage in materials for nuclear applications, including nuclear waste forms and nuclear reactor components. Two other microscopy-based techniques, in-situ liquid/gas cell electron microscopy (LC-EM) and Cryo-Electron Microscopy (CryoEM) are currently being used in several areas in materials research, including, catalysis research, battery development, and geochemistry.Nuclear materials, whether in a nuclear reactor or disposed thousands of meters underground in a geologic repository, are subject to internal atomic displacement damage and the interaction of radiolytic species at the material's interface. Developing the tools to