An energy-intensive multifunction cavitation process incorporating synchrotron X-rays (PXMEI-MFC) was used to treat the surfaces of the single-crystal Ni-based superalloys SC610 and CMSX-4, employing a mixture of water and heavy water. Similar to data previously obtained from PXMEI-MFC processing using a mixture of acetone and deuterated acetone, the efficiency with which SC610 could be modified was improved compared with that obtained using a laser-irradiated MFC process. However, the water/heavy water system provided a limited processing area compared with the acetone/deuterated acetone system and the alloy surface was not flattened. Although no further oxide film was added, the original oxide layer was not removed and the proportion of the γ' phase was not optimized. In addition, the structure-stabilizing elements Ta, W, and Re did not exhibit significant segregation. Nevertheless, the hardness of the processed region was increased to a greater extent than had been obtained in trials with the acetone/deuterated acetone mixture. Because the degree of processing was improved even with a heavy water concentration of just 1%, it is believed that, during processing of the SC610, heavy water produced higher cavitation collapse pressures and temperatures compared with non-deuterated water. In principle, based on adjusting the balance of various energy inputs, mixtures of heavy water and water should also enable optimization of the γ' phase proportion through self-organization and homogenization of the lattice structures of the γ' and γ phases, similar to mixtures of deuterated acetone and acetone.