Gene therapy and virotherapy are among the approaches currently used to treat malignant tumors. Gene therapy and virotherapy use a specific therapeutic gene that causes death in cancer cells. In early attempts at gene therapy, therapeutic genes were driven by ubiquitous promoters such as the CMV promoter, which induce non-specific toxicity to normal cells and tissues in addition to the cancer cells. Recently, novel cancer- and/or tissue-specific promoter systems have been developed to target cancer cells but not normal cells including stem cells. In this review, we describe cancer and/or tissue-specific gene therapy systems for the treatment of cancer. In particular, we will discuss three systems for gene therapy and virotherapy: i) tissue-specific promoter systems, ii) cancer-specific promoter systems, and iii) oncolytic virotherapy. We will also discuss the major challenges of cancer-targeting vector systems and future directions in this area.