Biomacromolecular therapeutic agents, particularly proteins, antigens, enzymes, and nucleic acids are emerging as powerful candidates for the treatment of various diseases and the development of the recent vaccine based on mRNA highlights the enormous potential of this class of drugs for future medical applications. However, biomacromolecular therapeutic agents present an enormous delivery challenge compared to traditional small molecules due to both a high molecular weight and a sensitive structure. Hence, the translation of their inherent pharmaceutical capacity into functional therapies is often hindered by the limited performance of conventional delivery vehicles. Polymer drug delivery systems are a modular solution able to address those issues. In this review, we discuss recent developments in the design of polymer delivery systems specifically tailored to the delivery challenges of biomacromolecular therapeutic agents. In the future, only in combination with a multifaceted and highly tunable delivery system, biomacromolecular therapeutic agents will realize their promising potential for the treatment of diseases and for the future of human health.