Large-scale processes that are modeled using differential algebraic equations based on mass and energy balance calculations at times require excessive computation time to simulate. Depending on the complexity of the model, these simulations may require many iterations to converge and in some cases they may not converge at all. Application of a storage and retrieval technique, named in situ adaptive tabulation or ISAT is proposed for faster convergence of process simulation models. Comparison with neural networks is performed, and better performance using ISAT for extrapolation is shown. In particular, the requirement of real-time dynamic simulation is discussed for operating training simulators (OTS). Integration of ISAT to a process simulator (CHEMCAD®) using the input-output data only is shown. A regression technique based on partial least squares (PLS) is suggested to approximate the sensitivity without accessing the first-principles model. Different record distribution strategies to build an ISAT database are proposed and better performance using the suggested techniques is shown for different case studies. A modified ISAT algorithm (mISAT) is described to improve the retrieval rate, and its performance is compared with the original approach in a case study. State estimation is a key requirement of many process control and monitoring strategies. Different nonlinear state estimation techniques studied in the past are discussed with their relative advantages/disadvantages. A robust state estimation technique like moving horizon estimation (MHE) has a trade-off between accuracy of state estimates and the computational cost. Implementation of MHE based ISAT is shown for faster state estimation, with an accuracy same as that of MHE. Flowsheet optimization aims to optimize an objective or cost function by changing various independent process variables, subject to design and model constraints. Depending on the nonlinearity of the process units, an optimization routine can make a number of calls for flowsheet (simulation) convergence, thereby making the computation time prohibitive. Storage and retrieval of the simulation trajectories can speed-up process optimization, which is shown using a CHEMCAD® flowsheet. Online integration of an ISAT database to solve the simulation problem along with an outer-loop consisting of the optimization routine is shown using the sequential-modular approach. / text