Background <p>The submental island flap (SIF) is a versatile reconstructive option for oral cavity defects, but concerns regarding recurrences in level I lymph node basins have persisted in the context of neoadjuvant immunochemotherapy (NICT). This study evaluated the clinical outcomes and the incidence of loco-regional recurrences following SIF reconstruction in patients with oral squamous cell carcinoma (OSCC) treated with or without NICT.</p> Methods <p>This retrospective cohort study included 279 patients who underwent SIF reconstruction for OSCC between 2018 and 2024, divided into NICT (<i>n</i> = 135) and upfront surgery (US, <i>n</i> = 144) groups. Propensity score matching (1:1) yielded 85 patients per group with balanced baseline characteristics. Primary outcome was loco-regional recurrence (LRR) analyzed using competing risks regression. Secondary outcomes included overall survival (OS), recurrence patterns, and flap-related complications.</p> Results <p>After matching, the NICT group demonstrated significantly less LRR (cumulative incidence 11.8% vs. 30.6%; Gray’s test, <i>p</i> = 0.004) and OS (3-year OS 91.8% vs. 85.7%; log-rank <i>p</i> = 0.041). On multivariable analysis, NICT remained an independent protective factor for LRR (adjusted SHR = 0.38; 95% CI: 0.20–0.72; <i>p</i> = 0.003) and OS (adjusted HR = 0.51; 95% CI: 0.27–0.96; <i>p</i> = 0.038). Critically, no recurrences occurred within level I or along the flap subcutaneous tract in either group. Pathological analysis confirmed complete level I lymph node clearance (median yield 7 nodes) with only two NICT patients having positive level I nodes. Flap complication rates were comparable between groups, with no total flap losses.</p> Conclusions <p>In this cohort, SIF reconstruction combined with meticulous level I lymph node clearance was feasible and not associated with observed level I or flap tract recurrences. NICT appears to be associated with significantly improved survival without compromising flap outcomes.</p>