Air filtration mechanisms in the composite filter media used in practical applications are important and challenging to understand because the component fibers could have various size scales and morphologies. In this work, a three-dimensional digital model of nanofiber-based filter media was reconstructed for the first time based on the X-ray tomography data for the cellulose substrate and the Focused Ion Beam-Scanning Electron Microscope (FIB-SEM) image analysis for the several microns thick (3.82-7.90 μm) electrospun polyvinylidene fluoride (PVDF) nanofiber membrane. Besides the high-resolution model where the details of the fibrous structures were fully resolved, another low-resolution model with approximated unresolved structures was also established. Filtration simulations utilizing these models were conducted considering the drag force, Brownian diffusion and aerodynamic slip. The simulated filtration efficiencies agreed well with the experiments for particles of 70-400 nm, including the most penetrating particle size (MPPS, 100-200 nm). Moreover, the structure-resolved models had higher accuracy but higher computational costs, while the unresolved simulations saved much running time but over-predicted the filtration efficiency, especially for smaller particles (<100 nm). Our study presents a comprehensive strategy for investigating the composite filter media with multiscale complex structures using a combination of advanced characterization technologies and modular simulation models.