<p>Developing an irradiation embrittlement predictive model for low-Cu reactor pressure vessel steels is essential for extending the life of modern pressurized water reactors. Irradiation-produced dislocation loops are recognized as the leading causes of embrittlement, surpassing the mechanism of Cu clustering with a reduction in Cu content in modern steels. Extensive data have been accumulated from surveillance programs on high-Cu steels used in old reactors. The extrapolation of these data to low-Cu systems for embrittlement prediction requires a comprehensive understanding of the interactions between Cu, particularly Cu-rich clusters, and radiation defects. Therefore, in this study, ab initio calculations of vacancy aggregation in solute clusters containing Cu, Ni, Mn, and Si were performed. The interactions between the solute elements and vacancies in the solute clusters and Fe matrix were analyzed. The results demonstrated the occurrence of attractive interactions between the Cu clusters and vacancies. The addition of Si and the synergistic effect between Ni and Mn facilitated vacancy aggregation in the solute clusters. The behavior of Mn correlated with its magnetic state, and the size effects of the solute elements were analyzed.</p>