This paper investigates the optimization of pressure vessels and separator internals through fluid dynamics and structural simulation techniques. In industries such as oil & gas, chemical processing, and petrochemicals, pressure vessels and separators are critical for ensuring safe, efficient, and cost-effective operations. As operational demands increase and regulations tighten, optimizing these systems for enhanced performance and reliability becomes imperative. Using advanced computational tools such as Computational Fluid Dynamics (CFD) and Finite Element Analysis (FEA), this paper explores methods for optimizing pressure vessel geometries and separator internals. The study highlights key optimization strategies, including the redesign of internal components to improve phase separation, reduce pressure drop, and minimize entrainment. Furthermore, structural simulations are used to analyze stress, fatigue, and buckling under dynamic loads, facilitating the reduction of material usage without compromising safety. Case studies demonstrate the practical application of these simulations in redesigning separator internals and optimizing pressure vessel wall and nozzle configurations. The integration of design tools into engineering workflows via CAD-CAE co-simulation and digital twin technologies offers significant advantages for real-time feedback and operational monitoring. The paper concludes with recommendations for best practices in incorporating simulations into the design and operational stages, emphasizing interdisciplinary collaboration and lifecycle analysis to ensure sustainable and efficient system designs.