<p>Core–multi-shell upconversion nanoparticles (UCNPs) highly doped with sensitizers and activators were synthesized by co-precipitation methods. With Zn²⁺ separately doped with Yb³⁺ or Ho³⁺ ions in different core–multi-shell structures, the nanoparticle morphologies, diffraction peak shifts, variations of upconversion luminescence&#xa0;(UCL) intensity and lifetime, underlying energy mechanisms, as well as multifunction potentials, were characterized and analyzed&#xa0;in detail. Lattice distortion promotes Yb³⁺ and Ho³⁺ 4f–4f transitions, but co-doping Gd³⁺ and Zn²⁺ ions in the NaHoF₄ matrix may induce offset of lattice distortion and lengthen the overall Yb³⁺–Ho³⁺ energy transfer distance. Zn²⁺-induced F⁻ vacancies can also quench energy as inner defects. And even in layers with identical content, the optimal Zn²⁺ doping can change with multi-shell structures. Besides, UCL intensity and lifetime may be non-positively correlated, especially in highly doped UCNPs with Zn²⁺ doping and multi-shell structures. With core-doped Zn²⁺ hetero-ions and controlled Yb³⁺ concentration, NaGdF₄:Yb³⁺@NaHoF₄@NaGdF₄:Yb³⁺ structures can achieve lifetimes as high as 635.82&#xa0;μs; while with core- or shell-doped Zn²⁺ hetero-ions, NaHoF₄@NaHoF₄@NaGdF₄:Yb³⁺@NaGdF₄:Yb³⁺ structures can achieve comparable UCL intensities with varied lifetimes ranging from 111.58 to 245.29&#xa0;μs. Multifunction characterizations manifested the high&#xa0;application potential of designed UCNPs in photo-induced bio-imaging and as contrast agents for both computed tomography and <i>T</i>₁/<i>T</i>₂-weighed magnetic resonance imaging. Our work can deepen the theory study of UCL finetuning with lattice distortion, and widen the multifunction application of NaHoF₄-based nanomaterials.</p> Graphical abstract <p></p>