Wastewater reclamation and reuse (WRR) is an emerging water generation tool for combating water stress. The objective of this paper is to develop a conceptual approach which will pave the way to WRR sustainable integration in a multi-resources regional or local system. For that purpose, a holistic Water Cycle Concept has been developed. The water cycle is devided into two partly overlapping circles: (a) Potable production circle, consisting of natural surface and ground water, desalinated water and rainwater, and (b) Recycled water circle, mainly for irrigation, industrial uses and streams rehabilitation. Greywater and direct potable use are developing options. The resulting water quality encounters are being analyzed, e.g. excess boron and magnesium deficiency in effluents originated from domestic desalinated water use are both detrimental to crops, lack of magnesium is also endangers soil stability and food nutrition value. Innovative technologies for complementing the holistic approach have been developed, e.g. minerals recovery from seawater and brine, electrochemical and natural processes hybridization for nutrients and hormones removal and biofilms prevention by nanoparticles injection. In conclusion, holistic water cycle approach enables management of water quality challenges and directs innovative solutions that protect food resources and eliminate long term threats of to public health.