Microwave hyperthermia (HT) is a promising adjunct therapy for breast tumors. This study investigates gold nanoparticle (GNP)-enhanced HT through three-dimensional electromagnetic (EM) simulation of a realistic breast phantom containing an embedded 5 mm tumor, excited by an eight-element fractal octagonal ring antenna (FORA) array operating at 2.45 GHz. A 5.85 nM concentration of 21 nm peptide-capped GNPs confined to the tumor region produces a 65–75$\%$ increase in peak specific absorption rate (SAR) and improves the target-to-breast quotient by 39–47$\%$ across both optimization methods, without introducing additional hotspots in healthy tissue. Two complementary optimization strategies are compared: Python-based genetic algorithm (GA) post-processing and direct optimization within CST. The Python/GA approach achieves a six- to seven-fold reduction in computational time (22–24 vs. 145–158 minutes), enabling rapid treatment planning for varying tumor geometries and nanoparticle concentrations. Baseline thermal modeling confirms that tumor temperatures reach 43–45$^\circ$C, within the therapeutic window for HT. These results demonstrate that GNPs effectively enhance EM energy focusing within the tumor region. The FORA antenna delivers the microwave energy, while the GNPs modify the target’s dielectric profile to selectively boost energy absorption-confining the heat to the tumor while safeguarding adjacent healthy tissue.’ Overall, this work provides computational evidence supporting the feasibility of GNP-enhanced microwave HT, while highlighting key optimization trade-offs between computational efficiency and protection of healthy tissue.