One of the most promising strategies for sustainable cancer eradication is immunotherapy, including the induction of the OX40/OX40L axis, a co‐stimulatory immune cell molecule interaction potentially creating cancer‐specific memory T cells for prolonged anti‐tumor responses.[47, 48, 49, 50] Therefore, we hypothesized that the injection of EVs actively loaded with murine Ox40L (mOx40L) mRNA into tumors of the highly aggressive B16F10 melanoma model would elicit a sustainable mOx40L display on tumor cells. The gene discussed is TNFSF4; the disease is melanoma.