In recent years, huge investigations on cancer progression and invasion have led to understand the pivotal role of tumor microenvironment. The current era of cancer therapy is based on the concept of simply targeting precise mechanisms to kill or to suppress the growth and expansion of malignant cells. Clinical data clearly correlate with in vitro results, emphasizing the direct impact of cancer environment on disease progression. This provides the opportunity to advance cancer therapy by virtue of targeting cancerous cells and non-cancerous component of tumor in a combinatorial manner. This tailor-made strategy demands the profound knowledge of cross talk between the biofactors of tumor environment and corresponding pharmacology of drug candidates. The neighborhood of tumor is critical for how cancer cells grow and invade surrounding tissues. It appears that the tumor microenvironment as a "co-op" includes malignant cells, blood vessels, immune/inflammatory factors and extracellular matrix. As a longstanding dilemma, it is well-proved that immune system plays a direct role in the existence and progression of such coop. In some cases, immune cells e.g. tumor associated macrophages (TAMs) infiltrate into tumor and instead of fighting cancer cells, support them to grow. As an important fact, this tumor complexity should not be taken as granted where it can be advantageous in cancer therapy as well as early detection and prevention. The central aim of this editorial article is to highlight the importance of tumor microenvironment for successful cancer therapy.