Salinity stress is a severe environmental stress that affects plant growth and productivity of potato, a strategic crop moderately sensitive to saline soils. Limited studies are available on the use of combined nano-micronutrients to ameliorate salinity stress in potato plants (Solanum tuberosum L.). Two open field experiments were conducted in salt-affected sandy soil to investigate plant growth, physiology, and yield of potato in response to soil salinity stress under single or combined application of Zn, B, Si, and Zeolite nanoparticles. It was hypothesized that soil application of nanoparticles enhanced plant growth and yield by alleviating the adverse impact of soil salinity. In general, all the nano-treatments applications significantly increased plant height, shoot dry weight, number of stems per plant, leaf relative water content, leaf photosynthetic rate, leaf stomatal conductance, chlorophyll content, and tuber yield, as compared to the untreated control. Furthermore, soil application of these treatments increased the concentration of nutrients (N, P, K, Ca, Zn, and B) in plant tissues, leaf proline, and leaf gibberellic acid hormone (GA3) in addition to contents of protein, carbohydrates, and antioxidant enzymes (polyphenol oxidase (PPO) and peroxidase (POD) in tubers. Compared to other treatments, the combined application of nanoparticles showed the highest plant growth, physiological parameters, endogenous elements (N, P, K, Ca, Zn, and B) and the lowest concentration of leaf abscisic acid (ABA) and transpiration rate. The present findings suggest that soil addition of the aforementioned nanoparticles can be a promising approach to improving crop productivity in salt-affected soils.