The current trends in population growth and consumption pattern remain to increase the demand for durum wheat grain. However, multiple biotic and abiotic challenges due to climate change coupled with crop management practices possess major concern to improve durum wheat production and storage proteins. Efforts on developing innovative agronomic and breeding strategies are essential to enhance productivity, and nutritional quality under the changing climate. Nitrogen is an important structural component of protein, and potentially reduce the adverse effect of drought stress through maintaining metabolic activities. Optimum nitrogen fertilization allows durum wheat producing farmers to attain high quality yield, brings economic benefit, and reduces environmental pollution. However, defining an optimum nitrogen fertilizer rate for specific location requires considering yield achievement and quality of the end products. If the producers interest is, geared towards production of high protein content, high nitrogen dose is required. If the interest gears towards grain yield improvement optimization of nitrogen fertilizer rate is important. This indicates that defining product-specific nitrogen application is required for sustainable durum wheat production. Therefore, future challenges of increasing production, productivity, and end-use functional properties of durum wheat will only be achieved through cooperation of multidisciplinary teams who are able to incorporate new technologies.