Plastic nanoparticles (PNPs) pose a threat to human health, as studies have suggested they have the ability to infiltrate tissues and disrupt cellular membranes. This study examines how lipid tail unsaturation and ionic environments impact interactions of polystyrene (PS) nanoparticles with model membranes. Three phospholipids (DOPC, POPC, and DPPC) were selected to represent varying degrees of unsaturation. Additionally, cations within the Hofmeister series (Ca2+, Mg2+, Na+, and K+) were examined for their effects. Total internal reflection fluorescence (TIRF) microscopy enabled visualization of diffusion behaviors and confinement of PS nanoparticles under these conditions. Furthermore, single-frame displacement (SFD) analysis of single particle trajectories and fluorescence correlation spectroscopy super resolution optical fluctuation imaging (fcsSOFI) analysis provided insight into nanoparticle diffusion and mobility dynamics. The findings highlight how both membrane composition and cationic environments may govern PNP interactions, offering key information into potential biological effects.