Abstract The purpose of this work is to investigate the utilization of a set of nanofluids as a coolant/moderator for Pressurized Water Reactor (PWR) APR 1400 PLUS7 assembly design through modeling their effect on essential neutronics parameters and quantities of interest via SERPENT with simplistic thermal-hydraulics feedback. Various scenarios are discussed including fresh and burned conditions as well as the effect of nanoparticles crud deposition. Al2O3, TiO2, and CNT water-based nanofluids with a range of concentrations in the span of 0.001 wt%–0.3 wt% were chosen for the present case study. For each nanofluid/concentration combination; the effect on the assembly’s multiplication factor, Fuel Temperature Coefficient (FTC), Moderator Temperature Coefficient (MTC), and the discharge burnup are studied and highlighted. Moreover, the effect of a CRUD-like deposition of the nanoparticles on the axial power shifts is studied via SERPENT.