Core-shell structural engineering is a common strategy for tuning upconversion luminescence in lanthanide-doped nanoparticles. However, epitaxial growth on hexagonal phase NaYbF4 nanoparticles typically suffers from incomplete shell coverage due to the large and anisotropic interfacial strain. Herein, we explore the effects of core particle size and morphology as well as reaction temperature on controlling the epitaxial growth of NaGdF4 shells on NaYbF4 nanoparticles with misfit parameters of fa = 1.58% and fl = 2.24% for axial and lateral growth, respectively. Rod-like core particles with a long length and a large diameter are found to promote shell growth with high surface coverage by facilitating the relaxation of lattice strains. Furthermore, the primary NaGdF4 shell can serve as a transition layer to mediate the growth of additional NaNdF4 coating layers that display an even larger lattice misfit with the core (fa = 2.98%; fl = 4.32%). The resultant NaYbF4@Na(Gd/Nd)F4 core-shell nanostructures simultaneously show strong multiphoton upconversion luminescence and superior magnetic resonance T1 ionic relaxivity. Our findings are important for the rational design of core-shell upconversion nanoparticles with optimized properties and functionality for technological applications.