Both system biology and cancer immunotherapy are emerging fields in life sciences research. Immunotherapy is considered as targeted treatment modalities for cancer. However, the complex nature of the tumor environment affects the efficacy and clinical outcome of this type of therapy. Combination therapy can be a solution. But this requires investigation at the cellular and molecular level of effect of the drugs. Systems biology is such a powerful tool, which allows the cellular level understanding and has been used in target discovery and validation in different fields of cancer research. Despite this advantage, challenges exist in large dataset mining. In this concluding chapter, we discuss some of the challenges and possible future directions that may help to overcome this problem.