The promise of (nano)biomaterials for the treatment of cancer can only be realized following a comprehensive scrutiny of the tumor microenvironment.The generic use ofinertvehicle that delivers a specific cargo to treat a range of cancer types and disease states obeys the one material fits all rule.However,this approach leads to suboptimal and unpredictable clinical outcomes.The key factors constructing the tumor milieu should guide the design of disease-responsive materials.