Significant progress toward this end has been achieved using ab initio simulations with various model systems. In previous studies, small cluster models encompassing only the metal nodes have been used to investigate the role of the metal center in MOFs. However, these small cluster models are often inadequate to model reactions in MOFs accurately because the catalytic behavior is determined not only by the metal center but also by the framework structure, which contributes to the confinement effect on product selectivity. To address this issue, periodic quantum chemical calculations have been applied to describe the extended structure of MOFs. Nevertheless, these simulations are computationally demanding for large unit cells, and the dipole-dipole interaction between periodic images may influence the quality of such calculations. Furthermore, handling periodic simulations with advanced hybrid functionals is challenging because of the difficulties in computing exact exchange. Recent advances in QM/MM simulations provide an appealing way to meet the balance between accuracy and computational costs. In QM/MM, only the reactant and a small region encompassing the active region are described by quantum mechanics, whereas the other atoms in the environment are described by classical force fields. This hybrid approach significantly reduces computational demands and has been effectively applied in modeling reactions in crystalline porous materials, such as zeolite and MOF catalysts.