In this century, water supply requirements for drinking, urban, and industrial applications are known as one of the most significant challenges facing humanity, so that if a sustainable solution is not found, it will become a severe crisis. Membrane technology is preferred compared to other separation technologies for water treatment due to its low cost, low energy requirement, easy operation and acceptable performance. Today, electrospun polymer nanofibers have been developed as one of the emerging and promising engineered materials for membrane synthesis due to a considerable high porosity, high permeate flux and selectivity, excellent physicochemical stability, and tunable properties. This review focuses on opportunities and challenges of water desalination and ion removal by mixed matrix electrospun nanofibrous membranes (abbreviated as mixed matrix ENMs), when are used as the individual membranes or the selective layers. Mixed matrix ENMs simultaneously benefit from the inorganic/organic micro/nano-particles dispersed into the polymeric nanofibrous matrices. Mixed matrix ENMs are a new generation of fibrous membranes that have recently received more attention not only compared to other membranes but also compared to their original ENMs because of their outstanding properties, such as designed pore size and its distribution, engineered surface chemistry, enhanced hydrophobicity/ hydrophilicity, porosity control, and increased flux and rejection efficiency. This review can shed some light on future researches for using mixed matrix ENMs for desalination and provide a road map for academic and R&D researchers with emphasis on sustainable development.