Developing effective mucosal vaccines is essential for inducing systemic and mucosal immunity against infectious diseases and cancer, yet low antigen stability remains a significant challenge. Herein, we developed a co-delivery platform utilizing a cationic polymeric nanoparticle (DA3), composed of secondary bile acid-conjugated polyethyleneimine, to encapsulate the TLR7/8 agonist resiquimod and ovalbumin antigen. The DA3/R848/OVA nanovaccine enhanced dendritic cell (DC) activation compared to control groups. In a B16-OVA melanoma model, the nanovaccine demonstrated strong therapeutic efficacy by suppressing tumor growth and establishing immunological memory. Notably, intranasal administration upregulated antitumor effects in metastatic lung tumor models and improved survival rates. These results demonstrate that the DA3-based co-delivery system is a viable strategy for overcoming mucosal barriers, offering a promising approach for needle-free vaccination and cancer immunotherapy