Flexible operation of coal-fired power plants is becoming increasingly necessary for successful integration of large-scale renewable power generation into the power grid. The maximum ramp rate and the number of load cycles are generally limited by the thermal stress experienced by the boiler pressure parts, turbine metallurgy and creep and fatigue of critical thick-walled components Main steam temperature is a critical operating parameter that must be controlled within acceptable limits for safe operation. Main steam temperature deviation beyond acceptable limit has impact on boiler pressure parts and turbine material of construction due to creep and fatigue effect. Base load operating units do not require steep ramp rate and hence recommended ramping rates are kept low within the safe operating zone in comparison to the flexible operation of the units with wide range load change width. Thermal stresses are caused by the temperature changes inside the thick-walled components and turbine steam admission parameters. Hence, the quality of main steam temperature control plays a vital role in flexible operation of the coal fired units. Conventional cascaded PID temperature control loop architecture performs well at steady state condition within a limited variation of load change at low ramp rate but it acts slowly and performs poorly at transient operating conditions of flexible operation of the boiler turbine with wide range load variation and load cycle with high ramp rate and remains far from rated conditions. In this paper, a Multi-Input Multi-Output (MIMO) Non-linear Model Predictive Control (MPC) design for regulation of the main steam temperature of a Once-Through supercritical Boiler is proposed. The controller is based on a non-linear dynamic model which incorporates dynamics of the variables of interest. It has the capability to operate effectively across a wide load range while maintaining main steam temperature within acceptable limits. A notable advancement in this design of MPC is the incorporation of coal flow demand and feedwater flow demand as additional control inputs alongside primary and secondary spray flows. In simulation test cases, the MPC controller demonstrates satisfactory performance and computational efficiency.