Decreased cellular uptake of drugs is a major factor that contributes to drug resistance, and this applies to both infectious diseases and cancer.1,2 Cell-penetrating peptides (CPPs) have emerged as a versatile class of delivery vectors capable of facilitating intracellular transport of diverse therapeutic cargos, including small molecules, proteins, and nucleic acids.3 The inherent biocompatibility and low immunogenicity of peptide-based systems make CPPs particularly attractive for targeted drug delivery applications. The ubiquitin-proteasome pathway is fundamentally conserved between mammals and fungi. This pathway leads to polyubiquitination of target proteins and their degradation by the 26S proteasome and thereby plays an important role in cancer biology. This pathway is tightly linked to the virulence of pathogenic fungi and their survival in host environments. This presentation highlights our research on the use of CPP-conjugated proteasome inhibitors that have shown promise as anticancer and antifungal agents.4