The knowledge of tumor microenvironment (TME) has grown exponentially in recent decades. TME is a complex milieu with an essential role in tumor formation, progression, metastasis, and treatment resistance. Dynamic and mutual crosstalk between the tumor cells controlling the TME and the nonmalignant cells leads to tumorigenesis. Despite the spectacular progress in cancer management, neoplasms are the second most common cause of mortality due to the lack of optimal response in many patients. The characteristic features of the TME include antitumor immune response suppression, hypoxia induction, metabolic reprogramming, formation of an acidic environment, mechanical alteration, and neural regulation. In this chapter, a concise introduction to the key subparts of the TME has been provided.