As part of the continuing search for more effective plant-wide control (PWC) system design methods, an integrated framework (IF) of heuristics and simulation has been proposed [Konda, N. V. S. N. M.; Rangaiah, G. P.; Krishnaswamy, P. R. Ind. Eng. Chem. Res. 2005, 44, 8300-8313], and has been successfully applied to the toluene hydrodealkylation process. This procedure makes effective use of rigorous steady-state and dynamic process simulation models to aid in decision-making during the development of the heuristic-based PWC structure. Though it is promising, there is still a need to test its applicability to other complex industrial processes. The present contribution considers the application of IF to the styrene monomer plant. The presence of heat-integrated adiabatic plug-flow reactors, a tall vacuum distillation column and a material recycle stream makes this process an ideal, challenging process for PWC study. The step-by-step application of the eight-stage IF procedure to the styrene plant is described. Two different structures, one with dual and the other with single composition control of distillation columns are developed. Their control performance for a variety of disturbances is analyzed using the dynamic disturbance sensitivity measure, settling time and profiles of key variables. Analysis of the results indicates that the procedure yields stable and robust control structures, and the structure with single composition control of the columns performs better. This is the first study to develop steady-state and dynamic simulation models, and complete PWC structures for the styrene plant, together with an evaluation of the IF methodology.