Metal nanoparticles (NPs) are suggested as a vaccine delivery platform. At present, there is limited description of cuboidal Ag nanocubes (AgNCs; nonporous) and Au nanocages (AuNCs; porous) as a protein carrier for vaccination. Here, the intrinsic protein binding ability of AgNC and AuNC is first investigated, using ovalbumin (OVA) as a model antigen, to determine its suitability as a vaccine carrier. Next, the effect of AgNCs and AuNCs on bone-marrow-derived dendritic cells (BMDCs) is assessed in vitro. Finally, in vivo humoral and cellular immune responses of AgNC–OVA and AuNC–OVA following intramuscular immunization and their prophylactic effects in B16F10-OVA mice tumor model are investigated. In terms of OVA loading efficiency, AgNCs are superior to AuNCs. Both nanomaterials are found not to induce BMDC maturation at subtoxic doses. After administration of nanovaccines, serum immunoglobulin G (IgG) responses are comparable between groups. However, there are slight alterations in relative frequencies of lymphocyte subpopulations, with AgNC–OVA-immunized mice exhibiting lower memory T cells and reduced B cell and T follicular helper cell populations in spleen. Overall, AgNC–OVA and AuNC–OVA immunizations do not alter tumor growth. This study characterizes the intrinsic immunomodulatory properties of AgNCs and AuNCs, as protein subunit vaccine carriers.