The tumor microenvironment (TME) is a complex and variable region characterized by hypoxia, low pH, high redox status, overexpression of enzymes, and high‐adenosine triphosphate concentrations. In recent years, with the continuous in‐depth study of nanomaterials, more and more TME‐specific response nanomaterials are used for tumor treatment. However, the complexity of the TME causes different types of responses with various strategies and mechanisms of action. Aiming to systematically demonstrate the recent advances in research on TME‐responsive nanomaterials, this work summarizes the characteristics of TME and outlines the strategies of different TME responses. Representative reaction types are illustrated and their merits and demerits are analyzed. Finally, forward‐looking views on TME‐response strategies for nanomaterials are presented. It is envisaged that such emerging strategies for the treatment of cancer are expected to exhibit dramatic trans‐clinical capabilities, demonstrating the extensive potential for the diagnosis and therapy of cancer.