Transcriptomics provides the tool for deciphering gene expression networks while proteomics link this network to protein products.  The third crucial partner is metabolomics that profiles metabolic networks for linkage to gene expression.  Modern NMR and mass spectrometry enable the broad screen analysis of the metabolome and their transformation pathways, transcending classical targeted metabolic studies.  We have combined these tools to investigate the anticancer mechanisms of different Se forms using human lung adenocarcinoma A549 cells as a model.  Using a combination of 2-D NMR, tandem-MS, and FT-MS we could map distinct perturbations of ¹³C labeling patterns in numerous metabolites induced by selenite and selenomethionine, including amino & organic acids, nucleotides, antioxidants, phospholipids (PL) and PL metabolites. The Metabolomics-Edited Transcriptomic Analysis ("META") approach was applied to selenite-induced changes in gene expression. The coupling of metabolic dysfunctions to altered gene expression profiles 1) provided new insights into the regulatory network underlying the metabolic dysfunctions; 2) enabled the assembly of disparate gene expression events into functional pathways; 3) revealed key protein targets for further proteomic analysis.  Hence, this approach can accelerate the resolution of the complex, form-specific anticancer mechanism of Se and is generally applicable to many other biological problems.