Bacterial therapeutics are promising delivery systems for cancer immunotherapy, capable of modulating the tumor microenvironment or delivering therapeutic payloads. However, systemic delivery without causing inflammation is challenging. Strategies include using LPS-deficient Salmonella typhimurium mutants to reduce inflammation, and approaches like vascular disruption agents (VDAs) to enhance bacterial access to tumors. VDAs such as CA4P improve tumor colonization by facilitating bacterial escape into tumors and inducing necrosis. Nanomedicine concepts, like the enhanced permeability and retention effect, can also aid bacterial accumulation in tumors. Removing existing tumor microbiomes may help therapeutic bacteria colonize tumors, though antibiotic use could have negative impacts on immunotherapy. External magnetic fields can guide bacteria to tumors, while synthetic gene circuits can control bacterial behavior and payload release. EcN and S. epidermidis are promising bacterial chassis for therapeutic applications. Engineered bacteria can deliver payloads such as cytokines, chemokines, and checkpoint inhibitors to enhance anti-tumor immunity. Biocontainment strategies, including synthetic auxotrophies and genetic code swapping, prevent uncontrolled bacterial growth and ensure safety. Future research aims to improve tumor colonization, controlled payload delivery, and biocontainment for effective cancer therapies.Bacterial therapeutics are promising delivery systems for cancer immunotherapy, capable of modulating the tumor microenvironment or delivering therapeutic payloads. However, systemic delivery without causing inflammation is challenging. Strategies include using LPS-deficient Salmonella typhimurium mutants to reduce inflammation, and approaches like vascular disruption agents (VDAs) to enhance bacterial access to tumors. VDAs such as CA4P improve tumor colonization by facilitating bacterial escape into tumors and inducing necrosis. Nanomedicine concepts, like the enhanced permeability and retention effect, can also aid bacterial accumulation in tumors. Removing existing tumor microbiomes may help therapeutic bacteria colonize tumors, though antibiotic use could have negative impacts on immunotherapy. External magnetic fields can guide bacteria to tumors, while synthetic gene circuits can control bacterial behavior and payload release. EcN and S. epidermidis are promising bacterial chassis for therapeutic applications. Engineered bacteria can deliver payloads such as cytokines, chemokines, and checkpoint inhibitors to enhance anti-tumor immunity. Biocontainment strategies, including synthetic auxotrophies and genetic code swapping, prevent uncontrolled bacterial growth and ensure safety. Future research aims to improve tumor colonization, controlled payload delivery, and biocontainment for effective cancer therapies.