Metabolite levels and their turnover rates are the main determinants of cellular metabolic state. Genetic regulation of metabolite levels can only be indirectly exerted through enzyme abundances, which are in turn regulated by various transcriptional, translational and post-translational mechanisms. Elucidation of the link between these regulatory mechanisms and metabolite concentrations is a fundamental challenge in systems biology. To this end, I will present a modeling framework that integrates transcriptomics/proteomics data within metabolic networks and the corresponding mass balance and kinetic constraints. Such a system-level analysis of metabolic networks can significantly contribute towards creating a sustainable (bio-) chemical industry; and for tackling complex, systemic diseases such as type-2 diabetes.