Tumorigenesis and metastasis are associated with metabolic reprogramming, including enhanced glycolysis and glutaminolysis. Recent developments in dynamic nuclear polarization (DNP) dramatically enhance the sensitivity of magnetic resonance spectroscopy, providing a novel method for metabolic imaging in real-time through 'hypersensing' of polarized metabolites. In parallel, advanced signal acquisition sequences, such as compressed sensing, improve spatial and temporal resolution providing better depiction of rapid metabolic events in small tumors and metastases. Here we review the potential of hyperpolarized magnetic resonance spectroscopy for studying the crosstalk between oncogenic cell signaling and metabolism, and for probing diagnostic biomarkers and metabolic indicators of therapeutic response in primary tumors and metastases.