A model representing the steady–state and dynamic behaviour of a Haber-Bosch ammonia plant was developed based on plant data from Croatian fertilizer company Petrokemija Plc. Kutina. The plant model was developed with the aim to study the performance of advanced control strategy and optimize the economic performance of the plant. Industrial ammonia plant within fertilizer production asset typically comprises eight highly integrated catalysed process steps with many process units, heat integration, and gas recycles. The intensive nature of the ammonia production process with many nested mass and energy streams makes it a significant challenge to design the appropriate control system. The objective of the research was to design an optimal control strategy based on the plant model. The model takes the main dynamic relationship between the ammonia production rate and other relevant process parameters in downstream and upstream units. As an additional feature, online monitoring of the reforming catalyst and reformer tubes performance in the steam–natural gas reformer as the main energy consumer of an ammonia plant was considered. In order to design an optimised advanced control system, the plant model was divided into three logical process units to reduce the computational effort needed for the optimal synthesis gas preparation, raw synthesis gas purification, and ammonia synthesis loop. With respect to achieving scientific contribution and subsequently practical implementation of the proposed control strategy, a custom advanced process control scheme has been developed that uses programmed cascade functions to predict and adjust critical process parameters in ammonia production. Specifically, it was developed an advanced ratio–cascade process control scheme, which provides efficient disturbance rejection. To reach an optimal economic level the ammonia production rate (set point) acts as the primary/master control loop while holding the steam–to–natural gas and air–to–natural gas molar ratios as secondary/slave controllers. To enhance the profit of the ammonia plant the economic profit objective function is proposed. Feedback from the profit function is used in the advanced process control scheme as an input to bring the ammonia plant operation to the maximum profitability level. The benefits of the developed process control strategy are more effective disturbances’ rejection, simplification of ammonia process control operation, and plantwide optimization of the overall ammonia plant. The developed model offers the opportunity to operate the plant with higher energy and throughput efficiency with more comprehensive insight into the operation of the catalysts and reformer tubes with the possibility to predict its lifetime. With the practical implementation of the proposed control scheme, an ammonia plant can increase profitability, availability, improve safety, and handle environmental related issues.