Multifunctional drug delivery systems (DDS) are in high demand for effectively targeting specific cells, necessitating excellent biocompatibility, precise release mechanisms, and sustained release capabilities. The hollow multishelled structure (HoMS) presents a promising solution, integrating structural and compositional design for efficient DDS development amidst complex cellular environments. Herein, starting from a Fe-based metal-organic framework (MOF), amorphous coordination polymers (CP) composited HoMS with controlled shell numbers are fabricated by balancing the rate of MOF decomposition and shell formation. Fe-CP HoMS loaded with DOX is utilized for synergistic chemotherapy and chemodynamic therapy, offering excellent responsive drug release capability (excellent pH-triggered drug release 82% within 72 h at pH 5.0 solution with doxorubicin (DOX) loading capacity of 284 mg g