Sequestration of CO2 in geologic reservoirs is one of the promising technologies currently being explored to mitigate anthropogenic CO2 emissions. Large-scale deployment of geologic sequestration will require seals with a cumulative area amounting to hundreds of square kilometers per year and will require a large number of sequestration sites. We are developing a system-level model, CO2-PENS, that will predict the overall performance of sequestration systems while taking into account various processes associated with different parts of a sequestration operation, from the power plant to sequestration reservoirs to the accessible environment. The adaptability of CO2-PENS promotes application to a wide variety of sites, and its level of complexity can be increased as detailed site information becomes available. The model CO2-PENS utilizes a science-based-prediction approach by integrating information from process-level laboratory experiments, field experiments/observations, and process-level numerical modeling. The use of coupled process models in the system model of CO2-PENS provides insights into the emergent behavior of aggregate processes that could not be obtained by using individual process models. We illustrate the utility of the concept by incorporating geologic and wellbore data into a synthetic, depleted oil reservoir. In this sequestration scenario, we assess the fate of CO2 via wellbore release and resulting impacts of CO2 to a shallow aquifer and release to the atmosphere.