Chemically robust, functional porous materials are imperative for designing novel membranes for chemical separation and heterogeneous catalysts. Among the array of potential materials, zirconium (Zr)-based metal–organic frameworks (MOFs) have garnered considerable attention, and have been investigated for applications related to gas separation and storage, and catalysis. However, a significant challenge with Zr-MOFs lies in their processibility, particularly in achieving homogenous thin films and controlling functional anisotropy. The recent developments in MOF thin film fabrication methodologies do not yield a solution to achieve mild reaction condition growth of Zr-MOF thin films with epitaxial MOF-on-MOF geometry (i.e. functional anisotropy). In the current work, we have devised a straightforward methodology under room temperature conditions, which enables epitaxial, oriented MOF-on-MOF thin film growth. This achievement is accomplished through a stepwise self-assembly approach involving Zr nodes and linkers on a functionalized substrate. This de novo developed strategy of functionality design is demonstrated for UiO-66 (University of Oslo) type Zr-MOFs. We have demonstrated the precise placement of chemical functionalities within the thin film structure, allowing for controlled chemical diffusion and regulation of diffusion selectivity.