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Nonspecific immunotherapies often induce general immune activation or suppression. Conversely, antigen‐specific immunotherapy, which refers to dampening or augmenting adaptive immunity against a disease‐specific antigen, increases T‐cell target specificity to pathological tissues, thereby reducing side effects on the rest of the immune system. Advances in engineering strategies for nanomaterials have enabled the feasible modulation of their physicochemical features to incorporate antigens and inherently interact with innate immune cells, which remarkably amplifies the orchestration of antigen‐specific immune responses against cancer and autoimmune diseases. From this contemporary perspective, the basic principles of antigen‐specific immunotherapy are briefly introduced and we elucidate how the latest nanoengineering paradigms regulate the functions of heterogeneous subsets of immune cells, such as antigen‐presenting cells, B cells, and regulatory or cytotoxic T cells, promoting antigen‐specific immunotherapy to treat autoimmune diseases and cancer. An outlook on prospects and remaining challenges have been discussed for, translating scientific discoveries of powerful nanomaterials into medical advances in antigen‐specific immunotherapy, thus offering new treatment modalities for patients with unmet needs. [ABSTRACT FROM AUTHOR]