Therapeutic antibodies and nanotherapeutic drugs are of great concern due to their widespread use against numerous diseases worldwide. They are frequently used for targeted therapy under the assumption that they cause fewer side effects than nontargeted drugs. Despite their specificity and particular design for therapeutic actions, they might still exhibit unintended adverse effects in the immune system. Immunotoxicity reactions are mediated by immunomodulation, including immunostimulation and immunosuppression. The present review gives an overview on the adverse immunotoxic effects induced by therapeutic antibodies as well as nanotherapeutic drugs. In this context, future methods combining more efficient drug design with better tolerability and fewer adverse effects are discussed to ensure improved safety in the engineering of therapeutic antibodies and nanotherapeutics.