Cancer is one of the major threat to human society, which is the second leading global cause of mortality after cardiovascular diseases. Most popular chemo-therapy and radiation-therapy have a significant impact on cancer treatment but till date, they are not successful in many advanced cases and metastatic stage of cancer. This leads the researcher to investigate new strategies to combat by selectively killing cancer cells without damaging normal cells. Viral oncotherapy is such a hopeful treatment option that offers an opportunity for targeting cancer cells. In this therapy, wild type or engineered oncolytic viruses are use to infect and destroy cancer cells by oncolysis. As a result of this new infectious viral particles are release to facilitate the destruction of the remaining cancerous cells. These viruses with anticancer activity can be designed in many ways and use in combination with other cancer therapy to increase their tumor selectivity and improve oncolytic activity. Here, we will discuss the strategies for oncolytic viral engineering with the mechanisms by which these viruses specifically kill tumor cells that make a promising modality for cancer therapy.