If appropriately selected for each patient, cancer peptide vaccines are highly specific and targeted to tumor cells. Unfortunately, the poor immunogenicity of peptide vaccines has limited their clinical utility and led to discontinuation of commercial development of several peptide vaccines in late clinical phases. Since peptides per se are completely non-immunogenic, co-treatment with immune adjuvant is always needed to initiate an immune response against tumor. The selection of adjuvant is critical since it defines the quality of immune response (meaning how “fit-for-fight” and empowered immune cells are, and which immune cell subpopulations are activated). Furthermore, peptide vaccines primarily induce a humoral immune response rather a than cellular immune response. A cellular immune response is required to eradicate tumors in cancer patients. Poor immunogenicity and the lack of local stimulatory effects in the tumor microenvironment, due to intradermal/intramuscular administration of peptides, are the main hurdles for the current peptide vaccine approaches.