The Levant basin in the southeastern Mediterranean has a very dynamic marine ecosystem. Although it is characterized by poor productivity, this sensitive ecosystem is also typified by high biodiversity and unique habitats. Sea water warming and extreme species invasion, mainly via the Suez Canal ("Lessepsian migration") make this ecosystem very dynamic. Man-made intense activities, including overfishing, accelerated coastal development (e.g., ports constructions, desalination and power plants, pollution, mariculture, shipping), natural gas exploration, utilization and transport in the deeper part of the inshore water caused considerable changes and threaten this fragile ecosystem.  In order to enhance ecosystem-based management of this complex environment, we identified the many stakeholders (coastal and off shore), and spatial and temporal conflicts between them and with the natural environment. Possible opportunities were recognized, such as enabling the use of the same marine space for several stakeholders while preserving the natural environment. E.g., marine areas that are closed to the public for security and operational reasons (naval bases, coastal portions of power and desalination plants) can be used as de-facto MPAs (Marine Protected Areas) and be added to natural marine reserves. Our study indicates that number of fish and macro-invertebrates species, biomass, and diversity index were always higher in such MPAs compare to control areas. Groupers, fishes of high commercial value, some of which are on the IUCN Red List of threatened species, were significantly more common and larger in this MPA. These no-fishing zones also protect the Mediterranean slipper lobster, another threatened species, and could serve also as a sanctuary for reproductive populations of these overfished species. We also recommend limiting fisheries, especially bottom trawling, in space, time and equipment and completely prohibit fishing during the recruitment season of the indigenous species (which is usually different from that of invading species). Expanding marine reserves to include various habitats, depths and bio-communities, with adequate critical mass of key species and connectivity with other reserves and considerable buffer zones between them and development activities will ensure the continuous of the ecosystem services of this environment. Yet the basis for a proper ecosystem-based management and planning is sufficient environmental and ecological knowledge of the habitat.  However this knowledge in the Levant Basin is only partial especially in the deep and open sea. It is often derived manly from the developers. For designing an objective marine spatial planning, there is a need for scientific and environmental marine data from independent sources.