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By 2030, the UN General Assembly issued the Sustainable Development Goal 6, which calls for the provision of safe drinking water. However, water resources are continuously decreasing in quantity and quality. NO 3 − is the most widespread pollutant worldwide, threatening both human health and ecosystems. NO 3 − separation systems (NSS) using IX and membrane-based techniques (MBT) are considered practical and efficient technologies, but the management of IX waste brine (IXWB) and concentrate streams for MBT (CSM), as well as the high salt requirements for IX regeneration, are challenging from both economic and environmental perspectives. It is essential to classify the different waste management strategies in order to examine the current state of research and identify the best option to address these issues. This review provides harmonized information on IXWB/CSM management strategies. This study is the first systematic review of all papers available in the Web of Science, Scopus, and PubMed databases published until February 2023. 75% of the studies focused on the use of biological denitrification (BD) and catalytic denitrification (CD). Although innovative technologies (bio-regeneration and direct CD) have advantages over indirect processes, they are not yet practical for large-scale plants because their reliability is unknown. Moreover, the generation of NH 4 + is the major challenge for application large-scale of chemical reduction. An innovative work flow diagram, challenges, and future prospects are presented. The review shows that integrating modified NSS with IXWB/CSM treatment is a promising sustainable solution, as the combination could be economically and environmentally beneficial and remove barriers to NNS application. [Display omitted] • The management strategies of the waste stream in NO 3 − separation systems reviewed. • Treatment options and/or minimization of waste stream systematically reviewed. • The economic and environmental benefits of brine reuse in IX are explained. • 75% of researches used biological (61%) and catalytic (14%) denitrification. • An innovative workflow diagram, obstacles, and future prospects are presented. [ABSTRACT FROM AUTHOR]