<p>Determining how anticancer drug-induced intratumor vascular damage alters drug permeability and enhances therapeutic efficacy is crucial for optimizing cancer treatment. This study successfully quantified anticancer drug encapsulated-MnO₂ (hollow PEGylated: H-MnO₂-PEG) nanoparticle (NP)-induced tumor vascular damage at the microscopic level by determining the vascular surface volume (based on surface smoothing) as well as the number and volume of vascular filaments using tumor transparency imaging. Variations in the drug permeability of H-MnO₂-PEG NPs encapsulating different anticancer drugs and the resulting tumor cell death were evaluated by quantifying tumor vascular damage. Interestingly, although the H-MnO₂-PEG nano drug carriers were identical, tumor vascular damage varied greatly depending on the encapsulated anticancer drug and its drug target. Moreover, the drug permeability and anticancer effect of the MnO₂ NPs also varied greatly. Specifically, vascular damage increased from 20.6 ± 2.4% (Dox) to 55.8 ± 1.6% (Ce6-PDT) and 73.0 ± 1.1% (Soraf), accompanied by corresponding increases in maximum cell death depth from 97.1 ± 1.8&#xa0;μm to 133.7 ± 8.2&#xa0;μm and 177.9 ± 13.3&#xa0;μm, respectively. In particular, H-MnO₂-PEG NP-mediated combination therapy of PDT and Dox chemotherapy significantly increased the drug permeability of H-MnO₂-PEG NPs owing to blood vessel damage caused by PDT, thereby showing a much greater anticancer effect than PDT and Dox chemotherapy together. This study presents, for the first time, that drug permeability and the resulting anticancer effect of nano drug carriers are greatly affected by intratumoral vascular damage through newly developed vascular damage models acquired based on vascular surface volume and the number and volume of vascular filaments.</p> Graphical abstract <p></p>