Lanthanide-doped upconversion nanoparticles have been the focus of a growing body of investigation because of their promising applications ranging from data storage to biological imaging and drug delivery. Here we present the rational design, synthesis, and characterization of a new class of core–shell upconversion nanoparticles displaying unprecedented optical properties. Specifically, we show that the epitaxial growth of an optically inert NaYF4 layer around a lanthanide-doped NaGdF4@NaGdF4 core–shell nanoparticle effectively prevents surface quenching of excitation energy. At room temperature, the energy migrates over Gd sublattices and is adequately trapped by the activator ions embedded in host lattices. Importantly, the NaYF4 shell-coating strategy gives access to tunable upconversion emissions from a variety of activators (Dy3+, Sm3+, Tb3+, and Eu3+) doped at very low concentrations (down to 1 mol %). Our mechanistic investigations make possible, for the first time, the realization of efficient emissions from Tb3+ and Eu3+ activators that are doped homogeneously with Yb3+/Tm3+ ions. The advances on these luminescent nanomaterials offer exciting opportunities for important biological and energy applications.