Optimal design and operation of MSF desalination process is considered here using MINLP technique within gPROMS model builder 2.3.4. gPROMS provides an easy and flexible platform to build a process flowsheet graphically and the corresponding master model connecting automatically individual unit model equations during simulation and optimisation. For different freshwater demand throughout the year and with seasonal variation of seawater temperature, the total annualised cost of desalination is minimised. It is found that seasonal variation in seawater temperature results in significant variation in design and some of the operating parameters but with minimum variation in of process temperatures. The results also reveal the possibility of designing stand-alone flash stages which would offer flexible scheduling in terms of the connection of various units (to build up the process) and efficient maintenance of the units throughout the year as the weather condition changes. In addition, operation at low temperatures throughout the year will reduce design and operating costs in terms of low temperature materials of construction and reduced amount of anti-scaling and anti-corrosion agents.