Recent research on translation and protein synthesis in several pathologies, including cancer, peripheral artery disease, and wound healing, demonstrates the key role played by translational factors in tumorigenic and angiogenic processes. This review will focus on one specific translational factor, eIF3e also called INT6, the "e" subunit of the translation initiation factor eIF3. INT6/eIF3e has recently been described as a multifunction protein playing a role in translation, protein degradation, DNA repair, nonsense-mediated mRNA decay, cell cycle and control of cell response to low oxygen (hypoxia or ischemia) through modulation of the Hypoxia Inducible Factors (HIFs). Interestingly, INT6/eIF3e is a double-edged sword that has both oncogenic and tumor suppressive abilities. In addition to its role in tumorigenesis, its silencing has recently been suggested as a potential therapeutic strategy to improve cell survival and function after ischemic injuries. Although a deeper understanding of the molecular mechanisms involved in these pathophysiological functions is essential, particularly to transform the in vitro/in vivo findings into clinical applications, INT6/eIF3e modulation could provide therapeutic benefit for a variety of human diseases such as cancer or vascular diseases.