Purpose <p>To evaluate the clinical impact of ¹⁸F-FDG PET/CT versus ⁶⁸Ga-FAPI-46 PET/CT in patients with advanced epithelial ovarian cancer (EOC), this study aims to investigate preoperative scoring criteria and establish a basis for the formulation of treatment plans tailored to this patient population.</p> Methods <p>A total of forty-one treatment-naive patients with advanced epithelial ovarian cancer were recruited for this study between July 2022 and February 2024. Each participant underwent both ¹⁸F-FDG and ⁶⁸Ga-FAPI-46 PET/CT imaging. The study compared the diagnostic accuracy, PET/CT parameters, tumor staging, and the guidance provided for clinical treatment decisions by these two imaging modalities. Additionally, the tumor burden as assessed by both imaging techniques was evaluated to predict the likelihood of achieving R0 resection in subsequent surgical procedures.</p> Results <p>In the context of peritoneal metastasis, various PET/CT parameters were analyzed, including Gross Tumor Volume (GTV), SUVmax, Total Lesion Glycolysis (TLG(FDG)), and Total Lesion-FAPI (TL-FAPI). The comparative analysis of the two imaging modalities revealed statistically significant differences (<i>P</i> &lt; 0.001). ⁶⁸Ga-FAPI-46 PET/CT showed a higher PCI score and better sensitivity than ¹⁸F-FDG PET/CT (<i>P</i> = 0.03). Notably, the diagnostic accuracy of ⁶⁸Ga-FAPI-46 PET/CT for detecting pelvic, para-aortic, and extra-abdominal lymph nodes was superior to that of ¹⁸F-FDG PET/CT, demonstrating enhanced sensitivity, specificity, and overall accuracy. Following the application of ⁶⁸Ga-FAPI-46 PET/CT, tumor stages were upgraded in 22% (9 out of 41) of patients, while 39% (16 out of 41) exhibited alterations in their PET/CT scores relative to ¹⁸F-FDG PET/CT. Furthermore, the implementation of ⁶⁸Ga-FAPI-46 PET/CT influenced treatment decisions in 17.1% (7 out of 41) of cases. For patients undergoing primary debulking surgery (PDS), receiver operating characteristic (ROC) curve analysis indicated that the GTV derived from both ¹⁸F-FDG PET/CT (AUC = 0.784, <i>P</i> = 0.018) and ⁶⁸Ga-FAPI-46 PET/CT (AUC = 0.809, <i>P</i> = 0.010), along with TL-FAPI (AUC = 0.809, <i>P</i> = 0.010), demonstrated predictive value for incomplete resection during EOC debulking surgery.</p> Conclusion <p>In comparison to ¹⁸F-FDG, ⁶⁸Ga-FAPI-46 PET/CT presents significant advantages in the detection of peritoneal and lymph node metastases, thereby providing a more accurate reference for the clinical staging of patients with advanced epithelial ovarian cancer. Importantly, ⁶⁸Ga-FAPI-46 PET/CT has the potential to modify treatment decisions in nearly 20% of patients, facilitating the selection of more appropriate therapeutic strategies.</p>