A large proportion of the payload delivered by nanoparticulate therapies is deposited not in the desired target destination but in off-target locations such as the liver and spleen. Here, we demonstrate that phototargeting can improve the specific targeting of nanoparticles to tumors. The combination of efficient triplet–triplet annihilation upconversion (TTA-UC) and Förster resonance energy transfer (FRET) processes allowed in vivo phototargeting at a safe irradiance (200 mW/cm2) over a short period (5 min) using green light.