To survive, cancer cells adapt their metabolism to sustain increased biomass production and bioenergetic demand as well as modulation of redox homeostasis. In addition, tumour proliferation often demands oxygen to the extent that the vasculature cannot supply, leading to tumor hypoxia. This condition selects for the most aggressive cancer clones, promoting increased metastasis, drug resistance and invasion. How cancer cells adapt their metabolism to survive at low oxygen tensions, and if this metabolic reprogramming contains targetable vulnerabilities is not completely understood. The aim of this thesis was to uncover metabolic vulnerabilities under low oxygen tensions, highlighting proline metabolism as a dysregulated pathway in hypoxic cancer cells.