Efficient energy transfer is a promising strategy in overcoming the inherent limits of a narrow band and weak absorption of lanthanide ions due to the nature of 4f-4f transitions. Herein, we introduce a nanoparticle-sensitized nanoparticle system where a near-infrared-emitting quantum dot (QD) is used as a sensitizer with broadband photon absorption for a lanthanide-doped nanoparticle (LNP) to generate second near-infrared (NIR-II) emission. The NIR-II luminescence of Er3+-doped LNP by Ag2S QD sensitization displays an enhancement of ∼17-fold in intensity and ∼10-fold in brightness over bare LNP because of increased absorptivity and overall broadening of the absorption spectrum of LNP. Furthermore, a QD-sensitized LNP system exhibits excellent photostability and is able to improve the signal-to-noise ratio of tumor NIR-II imaging via in situ cross-linking of QD and LNP. The QD-sensitized LNP system for luminescence enhancement opens a potential avenue for efficient energy transfer in complex nanoparticle-nanoparticle systems.