An off-the-shelf neoantigen vaccine targeting Lynch syndrome has demonstrated both safety and immunogenicity in clinical testing, marking a significant step toward preventing cancers in individuals with inherited genetic vulnerabilities. Lynch syndrome, caused by mutations in DNA mismatch repair genes, predisposes carriers to colorectal and other cancers with lifetime risks exceeding 80%. This represents a paradigm shift from treating cancer after it develops to immunologically preventing it in genetically susceptible populations. The vaccine approach leverages neoantigens—tumor-specific protein fragments that arise from the characteristic mutations in Lynch syndrome cancers. By priming the immune system to recognize these signatures before malignancy occurs, the strategy could theoretically eliminate nascent cancer cells. The implications extend beyond Lynch syndrome to other hereditary cancer syndromes like BRCA mutations, potentially transforming cancer care for millions. However, several challenges remain: determining optimal timing for vaccination, establishing long-term efficacy, and ensuring the immune response doesn't wane over decades. The approach also requires careful patient selection and monitoring, as preventive vaccines in healthy individuals demand exceptional safety profiles. While promising, larger trials with longer follow-up periods are essential before this preventive strategy can be widely implemented.