High resolution mass spectrometry (HRMS) leveraged with transient isotope labeling experiments has untapped potential to provide novel insights on context-specific metabolism, yet manual analyses are error-prone and laborious. Comprehensive mining and quantifying tools are needed. We describe Stable Isotope-assisted Metabolomics for Pathway Elucidation (SIMPEL), a tool to simplify analysis and interpretation of isotope enriched HRMS datasets. The efficacy of SIMPEL is demonstrated through examples of central carbon and lipid metabolism.