In this work, an intercomparison of sensitization effects produced by gold (GNP) and dextran-coated iron oxide (SPION-DX) nanoparticles in M059J and U87 human glioblastoma cells was performed using 6MV-photons. Three variables were mapped: the nanoparticle material, treatment concentration, and cell radiosensitivity. For U87, GNP treatments resulted in high sensitization enhancement ratios (SER10% up to 2.04). More modest effects were induced by SPION-DX, but still significant reductions in survival were achieved (maximum SER10%=1.61). For the radiosensitive M059J, sensitization by both NPs was poor. SER10% increased with the degree of elemental uptake in the cells, but not necessarily with treatment concentration. For GNP, where exposure concentration and elemental uptake were found to be proportional, SER10% increased linearly with concentration in both cell lines. For SPION-DX, saturation of sensitization enhancement and metal uptake occurred at high exposures. Fold change in the α/β ratios extracted from survival curves are reduced by the presence of SPION-DX but strongly increased by GNPs, suggesting that sensitization by GNPs occurs mainly via promotion of lethal damage, while for SPION-DX repairable damage dominates. The NPs were more effective in eliminating the radioresistant glioblastoma cells, an interesting finding, as resistant cells are key targets to improve treatment outcome.