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Tumor angiogenesis is a critical process that enables the progression and metastasis of solid tumors, including gastrointestinal cancer. The microenvironment of gastric cancer is characterized by hypoxia, which suppresses the ability of the immune system to fight cancer. Existing treatment regimens do not address this complication and consequently do not result in objective tumor shrinkage. Accordingly, new treatment strategies are urgently needed for gastric cancer. Targeted therapies and immunotherapy for some patients with advanced gastrointestinal cancer are new approaches to this difficult-to-treat cancer, which has not benefited from substantial therapeutic advances in recent years. We propose a new treatment strategy based on anti-angiogenic therapy for gastric cancer. Optimized anti-angiogenic therapy may relieve hypoxia and improve drug delivery, which would improve the anti-tumor immune response. In addition, we focus on the potential benefits of a combined approach using immune therapy and treatments designed for vascular normalization. This review emphasizes the potential for a new paradigm of immunotherapy aimed at modulating the tumor microenvironment to change clinical practice. Future research should identify patient populations that may benefit from this approach and quantify the synergistic effects of relevant therapies.