Nitrogen (N) is the most limiting nutrient for the production of vegetable crops, but anthropogenic sources pose risks due to its transformation into several reactive forms and movement throughout the environment. The bulk of the N research to date to improve Nitrogen Use Efficiency (NUE) has followed a reductionist factorial approach focused on synthetic N application rates and crop growth response, under monocultures. The increased adoption of diversified cropping systems, organic N sources, and alternative management practices makes it more challenging to unravel N form transformation, movement, and crop uptake dynamics, in time and space. Here, based on a selected review of the recent literature, we propose a holistic approach of nutrient management to highlight key management and production variables as well as multilevel cropping system, genetic, environmental, ecological, and socioeconomic interactions to improve the N cycle and NUE. The best management strategies to improve NUE include both organic and inorganic N rate calibration studies, germplasm selection, crop rotations, identification of nutrient x nutrient interactions, and pest and water management. Agroecological practices that may improve NUE include vegetational diversification in time and space, integrated crop–livestock systems, conservation tillage, organic amendment inputs, legume-based cropping systems, as well as a landscape approach to nutrient management.