Pembrolizumab and oncolytic viral therapy represent promising therapeutic strategies for improving outcomes in stage III esophageal cancer. This narrative review evaluates current clinical evidence regarding their efficacy and potential role in contemporary treatment paradigms. A comprehensive literature search was conducted using PubMed, Google Scholar and Web of Science to identify relevant studies published between January 2010 and December 2024. Emerging evidence suggests that pembrolizumab combined with chemotherapy demonstrates encouraging pathological response rates, particularly in esophageal squamous cell carcinoma. Oncolytic viral therapy has shown potential in enhancing tumour immunogenicity and improving local tumour control; however, clinical evidence remains limited. Most available data are derived from early-phase and non-randomised studies, underscoring the need for large randomised controlled trials.