Global plastic production reaches 400 MM tons each year, and the amount is projected to increase to 700 MM tons by 2030. Efficient polymer deconstruction/upcycling strategies are lacking and reflected in how nearly 80% of used plastics go to landfills. In this dissertation, computational methods were applied to explore catalytic and separation approaches for plastics upcycling. First, ab-initio density-functional theory calculations were used to model olefin cross-metathesis, used in tandem chemistry with alkane dehydrogenation, to convert polyethylene into fuel- and lubricant- range hydrocarbons. The metathesis cycle and several reactions for active-site formation were examined on a silica-supported tungsten-oxide catalyst. To understand the behavior of polyolefin/hydrogen mixtures confined in catalyst pores for hydrogenolysis processes, atomistic simulations were used to calculate the solubility of hydrogen in both bulk and confined polyethylene. For separations, specifically process modeling of adsorption-based separation, the Real Adsorbed Solution Theory was systematically evaluated using binary adsorption of ethanol/water in hundreds of zeolites. Here, ethanol/water is studied as a representative system to demonstrate how zeolites can separate azeotropic mixtures when traditional distillation is not efficient. Another separation process is examined for antioxidant/polymer mixtures using molecular dynamics where the objective is to reduce catalyst poisoning by removing antioxidants from melt-polymer streams. Overall, these studies contribute to an improved understanding of catalytic and separation-based methods to address the growing levels of used plastics while highlighting the broad capability of computational tools for modeling complex systems.