Immunomodulatory therapies have advanced to clinical trials over the past decade for the treatment of a range of diseases and disorders, from cancer to diabetes to transplant rejection. However, the efficacy of these therapies remains limited, as challenges associated with off-target drug toxicity, poorly controlled drug pharmacokinetics, and an incomplete understanding of real-time therapy responses prevent effective therapeutic windows from being realized. Here, we highlight some of our work on the design, fabrication, and characterization of biomaterial-based delivery technologies for the controlled delivery of immunotherapies and for the non-invasive monitoring of their associated immune responses for the treatment of cancer and autoimmune disease.