Metal-organic nanosensitizers (MONs), including nanoscale metal-organic frameworks (nMOFs) and nanoscale metal-organic layers (nMOLs), are emerging nanoplatforms for biomedical applications, including photodynamic therapy (PDT), radiotherapy-radiodynamic therapy (RT-RDT), immunotherapy, sonodynamic therapy, photothermal therapy (PTT), drug delivery, imaging, and sensing. MON is a crystalline, porous, and supramolecular material consisting of bridging organic molecules (ligands) and metal or metal-oxo nodes (primary or secondary building units). MONs can achieve efficient mass transport for drug delivery and energy transfer to sensitize the generation of reactive oxygen species (ROS), respectively. Because of the component hierarchy in MONs, we can incorporate photosensitizing molecules into the ligands for PDT or stabilize unstable drugs by framework rigidity. We can use heavy metals in the secondary building units (SBUs) to enhance radiotherapy (RT) or conjugate hydrophilic drugs to SBUs for a sustained release under physiological conditions. The insoluble, hydrophobic drugs can be loaded into the hydrophobic channels of MOFs for delivery or spatial isolation to avoid aggregation-induced quenching of photosensitizers (PSs).The research of MONs for drug delivery and cancer therapy is a cross-disciplinary research standing at the intersection of physics, chemistry, and biology. Physics is used to study the energy transfer and sensitization mechanisms as exemplified by how low-energy or high-energy photons interact with photosensitizers or heavy metal SBUs, respectively. Chemistry is used to efficiently synthesize and characterize MON materials with crystallinity, appropriate pore dimensions, and suitable particle sizes, and to modify MONs with suitable therapeutic motifs. Biology and immunology are used to identify target applications, analyze treatment outcomes, and inform MON optimization for enhanced biological effects. My Ph.D. thesis research further leveraged the properties of MON materials, such as the rigid framework, open channels, Lewis acidic SBUs, and material dimensionality to maximize their anticancer efficacy. Starting from molecular design and material engineering, my research interest gradually shifted to the biomedical applications of MONs and addressing the limitations of existing anticancer drugs, such as instability, limited water solubility, and poor pharmacokinetics. My graduate research demonstrates MONs as a powerful nanoplatform for rescuing unfavorable drug candidates to enhance cancer therapy, including PDT, RT-RDT, chemotherapy, and immunotherapy.