Cancer cells are optimized for survival and successful growth via processes that enable them to outcompete normal cells in their microenvironment. Many of these cellular adaptations are promoted by the pathophysiological hypoxia that arises in solid tumour development. Our work focuses on three essential components of tumour cell biology: (i) enhancement of nutrients/metabolites uptake, (ii) increased efficiency of nutrients utilisation via metabolic alterations and (iii) handling of metabolic waste production in a way that furthers their progression whilst hampering the survival of normal tissue. Hypoxia Inducible Factors (HIFs) act as essential drivers of these adaptations via the promotion of numerous membrane proteins including glucose transporters (GLUTs), monocarboxylate transporters (MCTs), amino-acid transporters (LAT1, xCT), and acid-base regulating carbonic anhydrases (CAs) and bicarbonate transporters (NBCs). These HIF-regulated proteins in turn interact with a host of other altered pathways in the pathophysiology of cancer. In addition to a competitive growth advantage for tumour cells, these HIF-regulated proteins are further implicated in metastasis, cancer ‘stemness’ and the immune response. We will provide evidence for a number of hypoxia-associated proteins that promote cellular energy production and the regulation of acid-base levels in tumour cells. Emphasis will be placed on current work manipulating multiple CA isoforms and NBCs, which are at an interesting crossroads of gas physiology as they are regulated by hypoxia to contribute to the cellular handling of CO2 and pHi regulation. Our research combined with others indicates that targeting of HIF-regulated membrane proteins in tumour cells will provide promising future anti-cancer therapeutic strategies. (Parts of this work have been discussed recently in Molecular Aspects of Medicine by Parks et al. 2016)