Background: High grade serous cancers (HGSC) of gynecological origin can be treated with neoadjuvant chemotherapy (NACT) and subsequent interval debulking surgery (IDS) when upfront surgery is not feasible. Chemotherapy response score (CRS) was proposed to evaluate on pathological specimens at IDS the response to NACT. Objective: We aim to assess survival outcomes stratified by CRS in HGSC patients and to explore interaction with residual disease (RD) after surgery. Methods: We identified all consecutive patients with HGSC at advanced stage (FIGO III–IV) that underwent NACT and IDS. We collected baseline data as well as survival data such as disease-free survival (DFS) and overall survival (OS). CRS was assessed on adnexal and omental specimens based on a three-tier classification. We conducted multivariate cox regression analyses of CRS classifications (CRS 1 vs 2 vs 3, CRS 1+2 vs 3 and CRS 1 vs 2+3) using RD as covariate. Results: We enrolled 47 patients with a median follow-up of 25 months (IQR: 11–78). RD after IDS failed to correlate with DFS (p = 0.73) and OS (p = 0.93). Adnexal CRS 2 (HR 0.4; 95% CI 0.2–1.0; p = 0.05) and CRS 3 (HR 0.30; 95% CI 0.11–0.65; p = 0.04) correlated with longer DFS. Moreover, CRS 2 (HR 0.12; 95% CI 0.04–0.33; p 0.01) and CRS 3 (HR 0.06; 95% CI 0.02–0.20; p 0.01) on adnexal specimens were significantly associated with improved OS. Neither the omental three-tier nor the two-tier classifications correlated with DFS and OS. Conclusions: CRS classification is apparently a simple and reproducible method. In our study the adnexal three-tier system correlate with DFS and OS independently from RD at IDS. Further studies are needed to clarify the clinical role of CRS classification.