Four different configurations of Multi-Effect-Desalination (MED): backward feed (BF), forward feed (FF), parallel feed (PF) and parallel/cross feed (PCF) are modeled in steady and dynamic operation to examine the behavior of these configurations under transient operation. Adding thermal vapor compressor (TVC) unit with the last effect of parallel/cross configuration is also studied and compared to the other configurations to show the advantage of this type of integration. The transient operation is achieved by applying ramp changes (disturbances) in the main input parameters that include steam flow rate at the heat source and cooling seawater temperature and flow rate at the heat sink. Steady state results indicate that parallel/cross feed has a relatively better performance characteristic than the other feed configurations regarding Gain Output Ratio (GOR) and specific heat consumption (SHC). Adding TVC unit to the parallel/cross feed achieves the lowest water production cost. Dynamic results show that MED-TVC with parallel/cross feed has the fastest response while backward feed and forward feed have the slower response to the applied disturbances. In the case of heat source disturbance, MED plants operating in the backward feed arrangement may be exposed to shut down due to the significant increase in brine level for the first effect. The MED-TVC process is susceptible to the heat sink disturbances compared to the PCF and other configurations. Also, changes in input parameters lead to the highest reduction in GOR for the MED-TVC process compared to the different configurations, especially for cooling seawater temperature. The highest reduction in brine level occurs in MED-TVC for a disturbance in the cooling seawater flow rate and may lead to MED-TVC evaporator drying condition. Hence, MED-TVC will require a reliable control system to avoid this type of plant operational disturbance.