Box Behnken Design is a factorial statistical approach that helps to overcome limitations associated with time-consuming full factorial experimental design. This study used the Box Behnken design and Design of Experiments (DoE) to develop the nebulized antiviral Camostat Mesylate loaded pegylated nanoliposomal suspension product with the target profile specifications of particle size <250 nm, polydispersity index (PDI) between 0.1 and 0.3, and zeta potential (ZP) of 0±5 mV, % entrapment efficiency (%EE) between 40%w/v to 70 % w/v and % drug loading between 20%w/w to 50%w/w. Box Behnken design with a robust standard least squares model was employed to develop the pharma product. Camostat Mesylate loaded pegylated nanoliposomal suspension was developed using the scalable ethanol injection method. The three independent factors at three levels were concentrations of the lipids employed to develop the formulation. Applying holistic QbD during formulation development using Design of Experiments (DoE) ensures a science-based, risk-managed approach to developing high-quality pharmaceutical products. The novelty in this investigation is that, for the first time, nebulized antiviral Camostat mesylate-loaded Nanoliposomes with a size of <250 nm, size <250 nm, polydispersity index (PDI) between 0.1 and 0.3, and zeta potential (ZP) of 0±5 mV, % entrapment efficiency (%EE) between 40%w/v to 70 % w/v and % drug loading between 20%w/w to 50%w/w were developed using DoE, Box Behnken Design, mathematical modeling and Response Surface Methodology.Furthermore, the Camostat mesylate-loaded Nanoliposomes were evaluated for inhibiting SARS-CoV-2 injection. Based on our findings, we kept other concentrations, i.e., Camostat Mesylate concentration at 2.25 mg/mL, 0.9%w/v NaCl, and 90%v/v ethanol and process parameters, namely, stirring speed, stirring time, ethanol addition rate, syringe diameter constant. From the mathematical modeling and Response Surface Methodology, we observed that the particle size of the nanosuspension increased with an increase in concentrations of DPPC and cholesterol. At the same time, increasing concentrations of DPPC increased the % entrapment efficiency and % drug loading; an increase in the concentration of Cholesterol led to a decrease in both those parameters. DoE successfully developed Camostat Mesylate loaded pegylated nanoliposomes with a particle size of 188 ± 0.75 nm, 75.47 ± 5.87 % entrapment of Camostat Mesylate and 49.65 ± 3.86 % drug load of Camostat Mesylate in liposomal product using the ethanol-injection method meeting target profile. The in vitro extended release of Camo from the Camo-pegNLs was observed in 24 h. The nebulized Camo-pegNL product showed MMAD of 4.01 ± 0.21 μm, GSD of 1.34 ± 0.03, and %FPF of 29.53 ± 6.5 %. In conclusion, integrating nebulized product development, Box Behnken Design, enabled the successful development of nebulized Camostat Mesylate loaded pegylated nanoliposomal suspension product, demonstrating their suitability for lung delivery of the antiviral drug.