BioresTAC introduces microenvironment-responsive activation: its protease-triggered design exploits dysregulated enzymes in tumors and inflamed tissues to restrict degradation activity to pathological niches. Preclinical validation in cancer and psoriasis models demonstrates enhanced efficacy with reduced off-target effects, establishing a dual-action paradigm—receptor-driven targeting and context-dependent activation—that redefines precision medicine for protein degradation therapies.