Heavy-metal-based nano-objects have been recently shown to act as radiosensitizers. One possible underlying mechanism causing this effect is the amplification of reactive oxygen species (ROS) production upon irradiation. This reaction could be utilized to improve radiotherapy by repolarizing M2 anti-inflammatory macrophages, which typically constitute the majority of the tumor-associated macrophage population, to the M1 pro-inflammatory phenotype that induces anti-cancer responses, as ROS upregulation has been associated with M1 polarization. This study employs gold nanoparticles (AuNPs) of sizes of 15 or 50 nm, coated with polyvinylpyrrolidone (PVP) or polyethylene glycol. These AuNPs upregulated M1 gene expression and favored the polarization effect of 5 Gy and 10 Gy X-ray irradiation but not of 5 or 10 Gy proton irradiation. Furthermore, 50 nm AuNPs coated with PVP reduced the survival of M2 co-cultured with pancreatic cancer cells, used alone or in combination with 5 Gy X-rays. The findings confirm that AuNPs combined with X-ray radiotherapy can repolarize TAMs to become more M1-like and cytotoxic to pancreatic cancer cells. This work presents an efficient and easy-to-manufacture technique to improve radiotherapy efficacy in solid cancers like pancreatic cancer.