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Our previous research has demonstrated that oncoVV-AVL, an oncolytic vaccinia virus engineered to carry the Aphrocallistes vastus lectin (AVL), exhibits potent cytotoxic effects on colorectal and hepatocellular cancer cells. Based on this foundation, we undertook a series of experiments to explore its efficacy on gastric cancer cells. Our findings revealed that oncoVV-AVL significantly increased reactive oxygen species (ROS) levels and suppressed the expression of NRF2, thereby enhancing viral replication and disrupting the cellular redox balance, ultimately leading to the demise of cancer cells. Additionally, our investigations uncovered that oncoVV-AVL reprogrammed the metabolic microenvironment to favor viral replication, culminating in the lysis of cancer cells. Furthermore, we observed that oncoVV-AVL not only regressed tumor growth but also induced tumor tissue necrosis. These promising results suggest potential new avenues for the therapeutic management of gastric cancer.