Multistage flash desalination (MSF) is at the forefront of energy-efficient and sustainable water provision, especially with solar energy. This study presents a comprehensive outdoor experimentation of a novel parabolic trough collector-integrated three-stage MSF system. The tests targeted at assessing the impact of various factors, such as varied flow rates and adjusted vacuum settings with/without nanofluid of CuO at 1 %wt, nanocoating, and both. The performance indicators included various system parameters: temperatures, distillation rates, recovery ratios, performance ratios, thermo-economic performance, and water quality. According to the findings, increasing brine flow rates boosted freshwater production but undesirably affected top brine temperature and output quality. That is why the highest daily freshwater output occurred at a flow rate of 30 L/h, while salinity was lowest at a flow rate of 10 L/h. Overall peak efficiencies were of 46.59 % (energy) and of 5.3 % (exergy). Increasing the vacuum inside the MSF chambers improved evaporation but caused brine carryover, negtively impacting the output water quality. Using a 1 %wt nanofluid of CuO enhanced the thermal characteristics, leading to a 17.4 % increase in productivity. Incorporating CuO nanocoating on condenser coils and collector evacuated tubes raised productivity by about 14.5 %, and combining it with CuO nanofluid upgraded this enhancement ratio to 24.29 %. The desalination system demonstrated competitive cost and productivity compared to similar systems.