Here, we showed EV‐mediated extrahepatic mRNA delivery at a dose at least one order of magnitude lower than currently used for LNP‐mediated mRNA delivery.[51] In fact, superior RNA delivery efficiencies in vivo by EVs as compared to LNPs has been reported previously using different EV engineering strategies.[24, 52, 53] Here, we successfully treated mice implanted with highly aggressive B16F10 melanoma with EVs loaded with effective cancer immunotherapy, the murine immunostimulatory co‐receptor Ox40L mRNA and protein. Here, TNFSF4 is linked to melanoma.