After local administration, PHOENIX can undergo programmable release of resiquimod (R848) and anti‐OX40 (aOX40) in the presence of abundant ROS: R848 is first released, causing a reduction of inhibitory MDSCs and TAMs, favoring breaking the chronic inflammation; aOX40 is subsequently transported into the TME and accelerates T‐cell activation and expansion even in the absence of TAAs, eliciting T cell‐mediated killing and generating neoantigens and leading to the reversal of tumor‐associated chronic inflammation. Here, TNFRSF4 is linked to neoplasm.