In recent years, considerable achievements have been made to motivate the construction of tumor microenvironment (TME)-specific functional nanomaterials, which can effectively respond to the inherent pathological and physicochemical conditions in diseased regions to improve the specificity of imaging and drug delivery. Until now, various nanoarchitectures have been designed to combat cancer effectively and specifically. This review summarizes the latest developments in TME-specific theranostic nanoplatforms based on multifunctional nanomaterials that hold potential for achieving the targeted recognition at tumor sites. Recent progress and achievements have also been summarized for nanosystems that can specifically respond to the TME with various stimulus-responsive strategies and their applications for drug delivery, diagnosis, treatment, and synergistic theranostics of cancer. This review emphasizes the significance of functional nanomaterials in response to tumor stimuli to enhance anticancer treatment efficiency and facilitate development in extensive research fields, including nanoscience, biomedicine, and clinical applications.