Waste from crustaceans has adverse effects on the environment. In this respect, shrimp waste was valorized for producing chitosan nanoparticles as a source for eco-friendly nano-nitrogen fertilizer. The application of nano-nitrogen fertilizers is a valuable alternative approach in agriculture due to its potential for reducing the application of mineral nitrogen fertilizers and increasing yield quality and quantity, thereby helping to reduce the worldwide food shortage. Chitosan nanoparticles were foliar sprayed at three volumes (0, 7, and 14 L/ha) and compared with mineral nitrogen fertilizer (M-N) sprayed at three volumes (0, 120, and 240 kg N/ha) and their combination on two wheat cultivars (Misr-1 and Gemaiza-11) during two consecutive seasons (2019/2020 and 2020/2021) in order to evaluate the agronomic response. The synthesized chitosan nanoparticles displayed characteristic bands of both Nan-N and urea/chitosan from 500–4000 cm−1. They are stable and have a huge surface area of 73.21 m2 g−1. The results revealed significant differences among wheat cultivars, fertilization applications, individual or combined, and their interactions for yield-contributing traits. Foliar application of nano-nitrogen fertilizer at 14 L/ha combined with mineral fertilizer at 240 kg/ha significantly increased total chlorophyll content by 41 and 31% compared to control; concerning plant height, the two cultivars recorded the tallest plants (86.2 and 86.5 cm) compared to control. On the other hand, the heaviest 1000-grain weight (55.8 and 57.4 g) was recorded with treatment of 120 kg Mn-N and 14 L Nan-N/ha compared to the control (47.6 and 45.5 g). The Misr-1 cultivar achieved the highest values for grain yield and nitrogen (1.30 and 1.91 mg/L) and potassium (9.87 and 9.81 mg/L) in the two studied seasons when foliarly sprayed with the combination of 120 kg Mn-N/ha + 14 L Nan-N/ha compared to the Gemaiza-11 cultivar. It can be concluded that Misr-1 exhibited higher levels of total chlorophyll content, spike length, 100-grain weight, grain yield in kg/ha, and nitrogen and potassium. However, Gemaiza-11 displayed higher biomass and straw yield values, plant height, and sodium concentration values. It could be economically recommended to use the application of 120 kg Mn-N/ha + 14 L Nan-N/ha on the Misr-1 cultivar to achieve the highest crop yield.