The pharmaceutical and biotechnology industries are in perpetual upheaval, dened by the unrelenting quest for creative techniques to improve treatment efcacy, reduce side effects, and improve patient outcomes. One such breakthrough has emerged as a game-changer in this pursuit throughout the years: PEGylation. This method, which includes the covalent attachment of polyethylene glycol (PEG) chains to various medicinal molecules, has proven to be an excellent tool for improv­ing the therapeutic potential of a wide range of medications. Its effectiveness is based on its capacity to change pharmacological properties such as solubility, stabil­ity, and circulation half-life while lowering immunogenicity and side effects. However, as the pharmaceutical and biotech sectors embraced PEGylation, a rising knowledge of its limitations and downsides emerged. The technology that was pre­viously marked as the pinnacle of drug delivery tactics now faces a fundamental challenge: moving “Beyond PEGylation”. This shift in attitude has ushered into a new era of drug delivery and therapeutic improvement innovation, inquiry, and reevaluation.