In the present article, the intermixing and clustering of U/Nd, O, and vacancies were studied by both laboratory and synchrotron-based x-ray diffraction in U1−yNdyO2−x alloys. It was found that an increased holding time at the high experimental temperature during initial alloy preparation results in a lower disorder of the Nd distribution in the alloys. Adjustment of the oxygen concentration in the U1−yNdyO2−x alloys with different Nd concentrations was accompanied by the formation of vacancies on the oxygen sublattice and a nanocrystalline component. The lattice parameters in the U1−yNdyO2−x alloys were also found to deviate significantly from Vegard's law when the Nd concentration was high (53%) and decreased with increasing oxygen concentration. Such changes indicate the formation of large vacancy concentrations during oxygen adjustment at these high temperatures. The change in the vacancy concentration after the oxygen adjustment was estimated relative to Nd concentration and oxygen stoichiometry.