Solid tumours possess unique microenvironment characterised by defective vessels, heterogeneous tumour cell, hypoxic regions, and anaerobic metabolisms. These often become intrinsic and acquired barriers to current therapeutical approaches, but they also create an ideal condition for the growth of anaerobic bacteria, which have shown specificity in their germination and multiplication. Spores from the strictly anaerobic clostridial had demonstrated ability in tumour specific colonisation and induction of tumour lysis following intravenous delivery. Clostridial strains genetically modified to act as "Trojan horse" gene therapy vectors have been developed. Similarly, recent development in immunotherapy strategies for cancer also utilizes gene transfer to facilitate a dormant host immune response directed against the tumour. Combination of anaerobic bacteria for cancer gene therapies with immunotherapy will probably be the most promising approach that can potentially generate a prolonged anti-tumour effect beyond the immediate treatment period of gene therapy, allowing for treatment of advanced primary tumours and disseminated disease. In this review, we introduce the recent understanding of tumour microenvironment and detail the advances in the use of anaerobic bacteria for cancer gene therapies and recent studies in immuno therapy for cancers. We believe that the use of combined treatment modalities of such will provide a rational paradigm to improve upon the clinical efficacy of cancer therapy.