Hypoxia is the principal architect of the topographic heterogeneity in tumors. Hypoxia-inducible factor-1α (HIF-1α) reinforces all hallmarks of cancer and donates cancer cells with more aggressive characteristics at hypoxic niches. HIF-1α potently induces sustained growth factor signaling, angiogenesis, epithelial-mesenchymal transition, and replicative immortality. Hypoxia leads to the selection of cancer cells that evade growth suppressors or apoptotic triggers and deregulates cellular energetics. HIF-1α is also associated with genetic instability, tumor-promoting inflammation, and escape from immunity. Therefore, HIF-1α may be an important therapeutic target in cancer. Despite that, the drug market lacks safe and efficacious anti-HIF-1α molecules, raising the quest for fully unveiling the complex interactome of HIF-1α in cancer to discover more effective strategies. The knowledge gap is even wider in gastric cancer, where the number of studies on hypoxia is relatively low compared to other well-dissected cancers. A comprehensive review of the molecular mechanisms by which HIF-1α induces gastric cancer hallmarks could provide a broad perspective to the investigators and reveal missing links to explore in future studies. Thus, here we review the impact of HIF-1α on the cancer hallmarks with a specific focus on gastric cancer.