The transition of immunotherapy administration from intravenous infusion to subcutaneous (SC) administration for oncology patients has garnered significant interest. SC administration offers multiple benefits, including at-home administration, enhanced patient compliance, reduced hospital congestion, lowered health care costs, and improved sustainability by reducing drug wastage and minimizing environmental impact. However, for many biologics, the shift to SC administration requires the development of ultra-high–concentration monoclonal antibody products (ultra-HCmAP) due to the need for large dose volumes. Here we explore the impact of the COVID-19 pandemic on immunotherapy administration and the imperative of adopting SC administration. We discuss challenges encountered throughout the manufacturing, shipping, storage and delivery of ultra-HCmAP. A central hurdle identified involves the physical instability and the exponential increase in viscosity of these biologics due to increased protein concentration. Both issues stem from molecular crowding that leads to elevated protein-protein interactions. The main excipients reported to reduce viscosity are salts and amino acids, with Arg-HCl demonstrating particularly improved formulation viscosity in ultra-HCmAP. However, excipients with viscosity-lowering effects can also impact protein stability. The journey to discover suitable excipient strategies remains ongoing, combined with emerging approaches such as molecular engineering and computational techniques, with the ultimate aim of facilitating the successful integration of SC administration for economic savings, environmental sustainability and social equity.