Purpose <p>We reviewed patients with resectable advanced OSCC who underwent curative surgery with or without NAC.</p> Methods <p>This study reviewed 159 patients (NAC, 58; no-NAC, 101 patients). NAC with docetaxel and nedaplatin was administered before curative surgery for cases suspected of OSCC with high clinical and histological malignancy. The impact of NAC on overall survival (OS), local, and latent metastasis was analyzed by uni- and multivariate analysis. A decision tree analysis was performed to explore cases where NAC is expected to be effective.</p> Results <p>N-classification and histologic differentiation significantly affected OS; NAC showed a near-significant impact, especially in invasive OSCC without nodal metastasis. On multivariate analysis, NAC and T-classification were significantly associated with local control, with NAC potentially effective for T4 or other invasive tumors; however, this association with local control did not translate into a significant difference in overall survival between the NAC and no-NAC groups. NAC did not prevent latent metastasis but had no negative effect on planned treatment.</p> Conclusion <p>In this retrospective single-center cohort, NAC administered before curative surgery was associated with improved local control in selected patients with advanced OSCC, particularly those with T4 tumors or high-grade histological invasion (Yamamoto–Kohama grade 4). However, this association did not translate into a significant overall survival benefit. The findings should be interpreted as hypothesis-generating given the observational design and substantial baseline imbalances between groups, and prospective validation is required before clinical recommendations can be made.</p>