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Pulmonary nodules are highly prevalent in adult human populations, with a substantial proportion representing dormant cancerous lesions. We hypothesized that these pulmonary dormant cancers debilitate in growth owing to the lack of an angiogenic switch in tumors. In this study, we comprehensively investigated the hypothesis that specific pathological triggers can activate this angiogenic switch utilizing severe acute respiratory coronavirus 2 (SARS-CoV-2) infection-induced hypoxia as a primary physiological stimulus. Our findings provide compelling experimental evidence demonstrating that SARS-CoV-2 infection induces profound pulmonary hypoxia and severe tissue inflammation in animal models. This microenvironmental disruption markedly upregulates the expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) within lung tissues. The resulting hyperactivation of the downstream VEGF-VEGFR2 signaling pathway effectively drives robust pulmonary neovascularization, a phenomenon frequently documented in clinical observations of COVID-19 patients. Furthermore, employing an established experimental tumor model, we demonstrated that SARS-CoV-2 infection directly accelerates tumor outgrowth via this specific VEGF angiogenesis-dependent cascade. Crucially, the targeted administration of a neutralizing antibody to block VEGF significantly suppressed tumor progression and outgrowth in SARS-CoV-2-infected, tumor-bearing animals. Our data show that the COVID-19-induced hypoxia-VEGF-angiogenesis axis serves as one of the mechanisms for initiating tumor outgrowth in pulmonary tissues.