Conventional cancer therapies, including chemotherapy, radiotherapy, and immunotherapy, have significantly advanced cancer treatment. However, these modalities often face limitations such as systemic toxicity, lack of specificity, and the emergence of resistance. Recent advancements in genetic engineering and synthetic biology have rekindled interest in using bacteria as a novel therapeutic approach in oncology. This comprehensive review explores the potential of microbial therapeutics, particularly bacterial therapies, in the treatment of cancer. Bacterial therapies offer several unique advantages, such as the ability to selectively target and colonize hypoxic and necrotic regions of tumors, areas typically resistant to conventional treatments. The review delves into the mechanisms through which bacteria exert antitumor effects, including direct tumor cell lysis, modulation of the immune response, and delivery of therapeutic agents like cytotoxins and enzymes. Various bacterial species, such as
Salmonella
,
Clostridium
,
Lactobacillus
, and
Listeria
, have shown promise in preclinical and clinical studies, demonstrating diverse mechanisms of action and therapeutic potential. Moreover, the review discusses the challenges associated with bacterial therapies, such as safety concerns, immune evasion, and the need for precise targeting, and how recent advances in genetic engineering are being used to overcome these hurdles. Current clinical trials and combination strategies with conventional therapies are also highlighted to provide a comprehensive overview of the ongoing developments in this field. In conclusion, while bacterial therapeutics present a novel and promising avenue in cancer treatment, further research and clinical validation is required to fully realize their potential. This review aims to inspire further exploration into microbial oncology, paving the way for innovative and more effective cancer therapies.