We report a topology-guided, precise insertion of three distinct secondary linkers into a zirconium-based metal-organic framework, NPF-300. Constructed from a tetratopic linker L and Zr-6 cluster, NPP-300 exhibits a unique scu topology and certain flexibility along the crystallographic a axis, and in conjunction with the conformation change of the primary ligand, is able to accommodate the stepwise insertion of three different secondary linkers along the a and c axes. Size-matching and mechanic strain of the resulting framework are two important factors that determine the chemical stability of the inserted linkers. Secondary linker insertion in NPF-300 significantly enables not only its porosity but also potentials to install up to three different functional groups for the construction of multivariate MOFs with homogeneity.