There are large variations in the reported efficiency of gold nanoparticle (GNP) radiosensitization. We have previously reported on a predictive model, which accounts for the detailed Auger and photoelectron tracks to calculate the cell survival probability. After validating our model using PC-3 cells incubated with 2 mg/ml of 30 nm GNPs and irradiated with 100 kVp or 300 kVp beams, we evaluated the interplay between photon energy, GNP size (1.9 and 100 nm) and sub-cellular localization. Experiments were in excellent agreement with the model. In predictive modeling, using a 100 kVp source and 1.9 nm nanoparticles, GNP localization had a significant impact on cell survival. A sensitizer enhancement ratio of 1.34 was achieved when GNPs were localized outside the cells, increasing to 2.56 when GNPs were also distributed in the cytoplasm and nucleus. Using a 300 kVp source, which emits photons mainly above the gold K-edge, the dependence on GNP localization and size was barely detectable, since long ranged electrons dominate the energy deposition. In summary, achieving intracellular uptake with targeted-GNPs can significantly enhance radiosensitization for photon energies below the gold K-edge, where Auger electrons contribute significantly to the local energy deposition. For higher energies, this is much less important.