Machine Learning (ML)'s growing role in process industries during the digitalization era is notable. This study combines Artificial Neural Networks (ANNs) and Aspen Plus to predict exergy efficiency, exergy destruction, and potential improvements in a cumene plant under uncertain process conditions. An optimization framework, using Particle Swarm Optimization (PSO) and Genetic Algorithm (GA), was developed to enhance exergy efficiency amid uncertainty. Initially, a steady-state Aspen model evaluates exergy efficiency, irreversibility, and potential improvements. The proposed model is transitioned to a dynamic mode, introducing artificial uncertainties into key variables. An ANN model predicts exergy efficiency and exergy destruction under uncertainty. The PSO and GA-based optimization methods improve exergy efficiency and reduce exergy destruction. This work demonstrates the potential real-time application of intelligent methods in plant analysis.