Over the course of use, both in-service and during storage, fuel claddings for nuclear reactors undergo complex changes that can drastically change their material properties. Exposures to irradiation, temperature changes, and stresses, as well as contact with coolant, storage pool, and dry storage environments, may induce microstructural changes, such as formation of radiation defects, precipitate dissolution, and chemical segregation, that can ultimately result in failure of the cladding if pushed beyond its limit. In order to predict the performance of cladding in-service and during storage, understanding of the dominant processes related to these changes and their consequences is essential. In situ transmission electron microscopy (TEM) allows dynamic observation, at the nanoscale, of microstructural changes under a range of stimuli, making it an excellent tool for deepening our understanding of microstructural evolution in claddings. This proceeding presents details of the new in situ ion irradiation TEM and in situ gas cell TEM capabilities developed at Sandia National Laboratories. In addition, it will present the initial results from both systems investigating radiation tolerance of potential Generation IV cladding materials and understanding degradation mechanisms in Zr-based claddings of importance for dry storage.