Among immune correlates of clinical responses, tumor-specificneoantigens took the spotlight as relevant targets for cancerimmunotherapy. The implementation of pipelines forpersonalized cancer therapy remains challenging due to theprivacy, that is patient-specificity, of neoantigens and the low-frequency of neoantigen-specific T cells in blood and tumorsamples. To overcome these obstacles, recent developmentsin the field of biotechnology have allowed the multiplexedidentification of neoepitope-specific T cells. This reviewaddresses the pros and cons of conventional neoantigenscreening methodologies and highlights the current as well asthe prospective biotechnological opportunities in the field.