Oxide dispersion-strengthened materials are reinforced by a (Y, Ti, O) nano-oxide dispersion and thus can be considered as nanostructured materials. In this alloy, most of the nanoprecipitates are (Y, Ti, O) nano-oxides exhibiting a Y2Ti2O7 pyrochlore-like structure. However, the lattice structure of the smallest oxides is difficult to determine, but it is likely to be close to the atomic structure of the host matrix. Designed to serve in extreme environments—i.e., a nuclear power plant—the challenge for ODS steels is to preserve the nano-oxide dispersion under irradiation in order to maintain the excellent creep properties of the alloy in the reactor. Under irradiation, the nano-oxides exhibit different behaviour as a function of the temperature. At low temperature, the nano-oxides tend to dissolve owing to the frequent ballistic ejection of the solute atoms. At medium temperature, the thermal diffusion balances the ballistic dissolution, and the nano-oxides display an apparent stability. At high temperature, the nano-oxides start to coarsen, resulting in an increase in their size and a decrease in their number density. If the small nano-oxides coarsen through a radiation-enhanced Ostwald ripening mechanism, some large oxides disappear to the benefit of the small ones through a radiation-induced inverse Ostwald ripening. In conclusion, it is suggested that, under irradiation, the nano-oxide dispersion prevails over dislocations, grain boundaries and free surfaces to remove the point defects created by irradiation.