The catalytic hydrogel membrane reactor (CHMR) is a promising new technology for hydrogenation of aqueous contaminants in drinking water. It offers numerous benefits over conventional three-phase reactors, including immobilization of nano-catalysts, high reactivity, and control over the hydrogen (H2) supply concentration. In this study, a computational model of the CHMR was developed using AQUASIM and calibrated with 32 experimental datasets for a nitrite (NO2−)-reducing CHMR using palladium (Pd) nano-catalysts (~4.6 nm). The model was then used to identify key factors impacting the behavior of the CHMR, including hydrogel catalyst density, H2 supply pressure, influent and bulk NO2− concentrations, and hydrogel thickness. Based on the model calibration, the reaction rate constants for the NO2− steady-state adsorption Hinshelwood reaction equation, k1 and k2, were 0.0039 m3 mole-Pd−1 s−1 and 0.027 (mole-H2 m3)1/2 mole-Pd−1 s−1, respectively. The reactant flux, which is the overall NO2− removal rate for the CHMR, is affected by the NO2− reduction rate at each catalyst site, which is in turn controlled by the available NO2− and H2 concentrations that are regulated by their mass transport behavior. Reactant transport in the CHMR is counter-diffusional. So for thick hydrogels, the concurrent concentrations of NO2− and H2 are limiting in the middle region along the x-y plane of the hydrogel, which results in a low overall NO2− removal rate (i.e., flux). Thinner hydrogels provide higher concurrent reactant concentrations throughout the hydrogel, resulting in higher fluxes. However, if the hydrogel is too thin, the flux becomes limited by the amount of Pd that can be loaded, and unused H2 can diffuse into the bulk and promote biofilm growth. The hydrogel thickness that maximized the NO2− flux ranged between 30 and 150 μm for the conditions tested. The computational model is the first to describe CHMR behavior, and it is an important tool for the further development of the CHMR. It also can be adapted to assess CHMR behavior for other contaminants or catalysts or used for other types of interfacial catalytic membrane reactors.