Engineered oral bacteria represent a promising approach in tumor microenvironment therapy. Despite decades of research, cancer remains a major global health issue, with oral microbes playing a significant role in cancer development and progression. Advances in bioengineering and nanotechnology have enabled the modification of natural bacteria to enhance cancer therapy. Engineered oral bacteria offer advantages such as targeted tumor delivery, genetic reprogramming, and the ability to produce and deliver anticancer agents. These bacteria exhibit favorable biosafety characteristics compared to traditional therapies. The human oral cavity, a rich microbiome, contains over 700 bacterial species and is linked to various cancers, including colorectal, pancreatic, and oral cancers. Recent studies highlight the potential of engineered oral bacteria in cancer treatment through mechanisms such as direct cytotoxicity, prodrug-converting enzymes, immune activation, and ROS production. These bacteria can be engineered to target cancer biomarkers, induce immune responses, and deliver therapeutic payloads. The application of engineered bacteria in tumor therapy includes oral, intravenous, and intratumoral administration routes, each with its own advantages and challenges. Clinical trials have shown promising results, with engineered bacteria demonstrating efficacy in immunotherapy and drug delivery. The role of oral microbiota in cancer is increasingly recognized, with Fusobacterium nucleatum being a key player in promoting cancer progression. Research continues to explore the potential of engineered oral bacteria in cancer treatment, aiming to improve therapeutic outcomes and reduce toxicity. The future of tumor microenvironment therapy may lie in the innovative use of engineered oral bacteria, offering new strategies for cancer prevention and treatment.Engineered oral bacteria represent a promising approach in tumor microenvironment therapy. Despite decades of research, cancer remains a major global health issue, with oral microbes playing a significant role in cancer development and progression. Advances in bioengineering and nanotechnology have enabled the modification of natural bacteria to enhance cancer therapy. Engineered oral bacteria offer advantages such as targeted tumor delivery, genetic reprogramming, and the ability to produce and deliver anticancer agents. These bacteria exhibit favorable biosafety characteristics compared to traditional therapies. The human oral cavity, a rich microbiome, contains over 700 bacterial species and is linked to various cancers, including colorectal, pancreatic, and oral cancers. Recent studies highlight the potential of engineered oral bacteria in cancer treatment through mechanisms such as direct cytotoxicity, prodrug-converting enzymes, immune activation, and ROS production. These bacteria can be engineered to target cancer biomarkers, induce immune responses, and deliver therapeutic payloads. The application of engineered bacteria in tumor therapy includes oral, intravenous, and intratumoral administration routes, each with its own advantages and challenges. Clinical trials have shown promising results, with engineered bacteria demonstrating efficacy in immunotherapy and drug delivery. The role of oral microbiota in cancer is increasingly recognized, with Fusobacterium nucleatum being a key player in promoting cancer progression. Research continues to explore the potential of engineered oral bacteria in cancer treatment, aiming to improve therapeutic outcomes and reduce toxicity. The future of tumor microenvironment therapy may lie in the innovative use of engineered oral bacteria, offering new strategies for cancer prevention and treatment.