Nanomaterials provide numerous advantages for the administration of therapeutics, particularly as carriers of immunomodulatory agents targeting specific immune cell populations during immunotherapy. While the physicochemical characteristics of nanocarriers have long been linked to their therapeutic efficacy and applications, focus has primarily been placed on assessing influences of size and surface chemistry. In addition to these materials properties, the nanostructure morphology, in other words, shape and aspect ratio, has emerged as an equally important feature of nanocarriers that can dictate mechanisms of endocytosis, biodistribution and degree of cytotoxicity. In this review, we will highlight how the morphological features of nanostructures influence the immune responses elicited during therapeutic immunomodulation.