Although medium and large scale solar desalination systems have been long been discussed and proposed as a sustainable root to offset water shortage in water-scarce areas, commercial units have not been introduced to the market, mainly due to inherent difficulties of part load operation under transient conditions and high costs of solar systems compared to conventional fossil-fired desalination. This study presents transient numerical analysis andtechno economic assessment of a concentrated solar thermal (CST) system to drive a Multi-Stage Flash (MSF) desalination plant with 5000 m3/day capacity. The dynamic performance of the CST system over a wide range of operation conditions is simulated and evaluated under varying weather conditions over one year for Mersa Matruhcity on the Mediterranean coast of Egypt, as a case study for the MENA region. A simplified cost analysis has been performed to explore the potential of CST-driven MSF and additionally for Reverse Osmosis (RO) desalination technology driven by concentrated solar power (CSP) in comparison with fossil-fired desalination. It has been found that the desalinated water cost of CSP-RO is competitive with fossil-fired systems, while the associated cost of CST- MSF is approximately 3 times more costly than both CSP-RO and fossil-fired systems, without the cost of CO₂ capturing and storage for fossil-fired systems.