This study aimed to evaluate the ability of 18F-FDG-PET/CT to predict pathological complete response (pCR) in lesions of patients with advanced epithelial ovarian cancer (EOC) following neoadjuvant chemotherapy (NACT). We assessed whether 18F-FDG-PET/CT could predict lesion-specific pCR prior to interval debulking surgery (IDS), thus guiding precise lesion resection. Twenty-four patients with advanced EOC underwent IDS after NACT. 18F-FDG-PET/CT imaging was performed before and after NACT, with the maximum standardized uptake value (SUVmax) recorded for each metabolically active site. The relationship between the relative change in SUVmax (ΔSUVmax) of grossly visible or suspicious lesions resected during IDS and their pCR status was analyzed. Additionally, the association between omental ΔSUVmax and the chemotherapy response score (CRS) and CA125 elimination rate constant K (KELIM) score was examined. Tumor lesion ΔSUVmax Post-NACT was significantly associated with pCR (P < 0.001, odds ratio [OR] 0.001, 95% confidence interval [CI]: 0.000-0.012). A reduction in SUVmax > 60.2% predicted pCR in lesions (sensitivity 75.6%, specificity 79.2%), with an area under the curve (AUC) of 0.817 (95% CI: 0.756-0.877, P < 0.05). Site-Stratified analysis showed that reductions > 59.6% in peritoneal implants (sensitivity 71.4%, specificity 95.7%, AUC 0.905, 95% CI: 0.821-0.989, P < 0.05), > 63.95% in metastatic lymph nodes (sensitivity 72.7%, specificity 94.4%, AUC 0.904, 95% CI: 0.815-0.994, P < 0.05) predicted pCR at respective sites, and reductions > 73.9% in primary lesions (sensitivity 100%, specificity 78.9%, AUC 0.816, 95% CI: 0.642-0.990, P = 0.151) predicted a trend toward significance in pCR results. Omental ΔSUVmax differed significantly between CRS1/2 and CRS3 groups (t = 3.404,P = 0.003); a reduction > 49.95% predicted CRS3 (sensitivity 83.3%, specificity 78.6%, AUC 0.893, 95% CI: 0.736-1.000, P < 0.05). Omental ΔSUVmax was positively correlated with the KELIM score (r = 0.712, P < 0.001), and primary lesion ΔSUVmax was also significant associated with KELIM score (r = 0.547, P = 0.015). 18F-FDG-PET/CT can predict lesion-specific pCR after NACT in advanced EOC, providing guidance for the extent of IDS.