The global spread of COIVD-19, as well as the worsening air pollution throughout the world have brought tremendous attention into the development of materials that can efficiently capture particulate matter (PM). Traditional filters made from fabric, glass fibers, or melt blown fibers exhibit a low efficiency at removing sub-micrometer and nanoscale particles. Additionally, they exhibit limited performance in high humidity, high temperature environments. We suggest that the high porosity of filters composed of nanofibers could provide minimal obstruction to air flow, while their high tortuosity and surface area-to-volume ratio presents an excellent platform for particle capture. Electrospinning is a simple and well-studied process to produce randomly accumulated nano- and micro-scale diameter fibers. The main advantages of electrospun nanofibers include their tunable fiber morphology and diameter under specific electrospinning parameters, as well as the ease of post-process modification. Studies have demonstrated its promising applications ranging from tissue engineering, water purification to wearable electronics. Giving the tunable aspect of the process, various polymers were electrospun with different morphology and fiber diameter which all demonstrated high particle removal efficiency. Cellulose was chosen as the base material for our study since it is the most abundant biopolymer and its affinity for further chemical modification. In this study, the removal of nanoscale particles via in-house fabricated cellulose nanofilters is significantly enhanced by chemically functionalizing the fibers’ surface via the deposition of the bio-inspired glue polydopamine (PDA) and the polycation poly(diallyldimethylammonium chloride) (PDADMAC). Nanofilters were electrospun from cellulose acetate solutions before being regenerated to cellulose via an alkaline treatment. Cellulose nanofilters were then functionalized using only PDA or the codeposition of PDA with PDADMAC. Scanning electron microscope (SEM), Fourier transform infrared spectrometer (FTIR), and high-resolution X-ray photoelectron spectroscopy (XPS) were used to characterize the nanofilters. The effects of filter packing density, filter layering, and surface functionalization on their performance, i.e., their filtration efficiency, most penetrating particle size (MPPS), performance in a high humidity environment, and filter pressure drop were investigated. Furthermore, by introducing hydrophilic and hydrophobic nanofibers within a composite filter structure, the performance of the composite filter remained unchanged even in high humidity.