As potential nuclear waste host matrices, two series of uranium-doped Nd₂Zr₂O₇ nanoparticles were successfully synthesized using an optimized molten salt method in an air atmosphere. Our combined X-ray diffraction, Raman and X-ray absorption fine-structure (XAFS) spectroscopy studies reveal that uranium ions can precisely substitute the Nd site to form an Nd_2–x U _x Zr₂O_7+δ (0 ≤ x ≤ 0.2) system and the Zr site to form an Nd₂Zr_2–y U _y O_7+δ (0 ≤ y ≤ 0.4) system without any impurity phase. With increasing U concentration, there is a phase transition from pyrochlore (Fd 3 m) to defect fluorite (Fm 3 m) structures in both series of U-doped Nd₂Zr₂O₇. The XAFS analysis indicates that uranium exists in the form of high-valent U⁶⁺ in all samples. To balance the extra charge for substituting Nd³⁺ or Zr⁴⁺ by U⁶⁺, additional oxygen is introduced accompanied by a large structural distortion; however, the Nd₂Zr_1.6U_0.4O_7+δ sample with high U loading (20 mol%) still maintains a regular fluorite structure, indicating the good solubility of the Nd₂Zr₂O₇ host for uranium. This study is, to the best of our knowledge, the first systematic study on U-incorporated Nd₂Zr₂O₇ synthesized via the molten salt method and provides convincing evidence for the feasibility of accurately immobilizing U at specific sites.