Engineering Coordination-Defined Metal–Phenolic Networks: From Molecular Self-Assembly to System-Level Platforms for Advanced Tumor Therapy

• This review introduces recent advances in the design of MPN-based nanoplatforms. • This review discusses the application of MPN-based nanoplatforms in tumor therapy. • This review analyzes the challenges faced by MPN-based nanoplatforms. Metal-phenolic networks (MPNs), constructed through the dynamic coordination between metal ions and phenolic ligands, have emerged as a premier class of architecture-defined nanomaterials for precision oncology. Shifting away from conventional reviews that primarily catalog formulation strategies or biointerface coatings, this review uniquely adopts an architecture- and coordination-defined perspective to systematically elucidate how the hierarchical programming of metal–ligand bonds and network topology dictates the evolution of MPNs from simple passive nanocarriers into autonomous, integrated 'system-level' platforms. By bridging molecular coordination variables-such as metal lability and ligand denticity-with macroscopic functional outcomes-including catalytic kinetics and energy transduction efficiency. Beyond functional performance, this work provides a critical analysis of the clinical-translational interface, addressing pivotal constraints such as coordination stability, metabolic fate, and regulatory interpretability. Furthermore, we explicitly define the evidentiary standards required to differentiate generalized oxidative stress from pathway-specific regulated cell death, such as ferroptosis and cuproptosis, ensuring scientific rigor in translating these nanoplatforms from laboratory-scale synthesis to predictable and controllable clinical cancer therapeutics.