Physicochemical properties of polymers strongly depend on the arrangement and distribution of attached monomers. Templated polymerization using porous crystalline materials appears as a promising route to gain control on the process. Thus, we demonstrate here the potential of metal−organic frameworks as scaffolds with a versatile and very regular porosity, well adapted for the regioselective oxidative polymerization of pyrene. This photoresponsive monomer was first encapsulated within the one-dimensional (1D) microporosity of the robust zirconium(IV) carboxylate metal−organic framework (MOF) (MIL-140D) to, later, undergo in situ oxidative polymerization, enabling the growth of a highly selective polypyrene (PPyr) regioisomer over other potential polymer configurations. To confirm the polymerization and the geometry control of pyrene, the resulting composites were exhaustively characterized by powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), N 2 sorption measurements, scanning transmission electron microscopy coupled with energy-dispersive X-ray (STEM-EDX) spectroscopy, and fluorescence spectroscopy. Among others, photoluminescence quenching and emission shift in the solid state demonstrated the presence of PPyr inside the MOF porosity. Furthermore, an in-depth joint analysis combining solid-state, magic-angle spinning (MAS) 1 H and 13 C NMR spectroscopy, Fourier transform infrared (FTIR) spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS), and molecular simulations (grand canonical Monte Carlo (GCMC) and density functional theory (DFT)) allowed the elucidation of the spatial, host−guest interactions driving the polymerization reaction.