The Novo Nordisk Foundation Center for Biosustainability (CFB) is a new non-profit research center focused on sustainable production of biochemicals and therapeutic proteins using microbial and mammalian cell factories. The work at CFB is organized around an iterative loop where cell factories are taken through four stages: 1) In silico design and data analysis, 2) genome engineering, 3) characterization and high throughput screening, and 4) omics based systems analysis. However, before entering this loop, significant two significant decisions need to be made. First, the choice of what products should be made should be made considering biological, technical, economic, and ecological factors. Second, the choice which platform strains will be used to develop production hosts should be made based on characterization of both metabolic and process tolerance traits of strains. I will discuss the role of modeling and systems biology approaches in guiding both the product and strain selection processes.