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Established oral squamous cell carcinoma (OSCC) remains constrained by local recurrence, inadequate lesion exposure, systemic toxicity, and therapy resistance. This narrative review evaluates a proposed microneedle-small extracellular vesicle (sEV) system for localized adjunctive treatment in three preclinical contexts: postoperative residual-disease control, local immunomodulation/checkpoint combination, and chemoradiotherapy sensitization. Direct evidence for the combined microneedle-sEV system in OSCC is not yet available; the analysis therefore integrates OSCC-specific sEV mechanisms with oral-mucosal microneedle and cross-disease engineering studies. We focus on whether the proposed microneedle-sEV system can preserve sEV potency, achieve reproducible local delivery, and meet oncologic-safety, manufacturing, and repeated-dose oral-safety requirements. The review provides a preclinical decision framework and comparator-based development criteria rather than a claim of clinical readiness.