Malignant transformation and sustained growth of tumors profoundly alter the tumor microenvironment, including angiogenesis, metabolism, immune response, and oxygen levels. In turn, remodeling of the tumor microenvironment can effectively promote tumor progression and hinder drug delivery, which is a prerequisite to the therapeutic efficacy of anticancer drugs. Moreover, the components of the tumor microenvironment mutually regulate each other, which further contribute to the complexity of cancer biology. This chapter aims to overview the causes and outcomes of abnormal tumor vascularization, metabolism reprogramming, immune evasion, endoplasmic reticulum stress and unfolded protein response, and hypoxic conditions in tumors. We will also briefly discuss the complicated interplay between these components of the tumor microenvironment.