The article presents a novel approach to targeted cancer therapy using extracellular vesicles (EVs) decorated with antibody-binding moieties specific for the fragment crystallizable (Fc) domain. The authors engineered EVs to be capable of binding to different types of immunoglobulin G antibodies, allowing them to target various tissues of interest. Through optimization, they demonstrated that these Fc-EVs can be targeted to cancer cells expressing human epidermal growth receptor 2 (HER2) or programmed-death ligand 1 (PD-L1), leading to reduced tumor burden and improved survival in mice with subcutaneous melanoma tumors. The Fc-EVs were also loaded with the chemotherapeutic drug doxorubicin, showing enhanced cytotoxicity. The technology is versatile and can be adapted to display other Fc-fused proteins, bispecific antibodies, and antibody-drug conjugates, making it a promising tool for targeted cancer therapy.The article presents a novel approach to targeted cancer therapy using extracellular vesicles (EVs) decorated with antibody-binding moieties specific for the fragment crystallizable (Fc) domain. The authors engineered EVs to be capable of binding to different types of immunoglobulin G antibodies, allowing them to target various tissues of interest. Through optimization, they demonstrated that these Fc-EVs can be targeted to cancer cells expressing human epidermal growth receptor 2 (HER2) or programmed-death ligand 1 (PD-L1), leading to reduced tumor burden and improved survival in mice with subcutaneous melanoma tumors. The Fc-EVs were also loaded with the chemotherapeutic drug doxorubicin, showing enhanced cytotoxicity. The technology is versatile and can be adapted to display other Fc-fused proteins, bispecific antibodies, and antibody-drug conjugates, making it a promising tool for targeted cancer therapy.