The global rise of difficult-to-treat resistance (DTR) bacteria, such as Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae (KPC-Kp), poses a critical challenge in controlling infections and curbing the spread of antimicrobial resistance genes. Antimicrobial photodynamic inactivation (aPDI) offers a promising alternative to traditional antimicrobials by effectively targeting extensively drug-resistant pathogens and mitigating antimicrobial resistance. This study investigated the in vitro photodynamic efficacy of the cationic porphyrin 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP) against planktonic cultures of KPC-Kp. The minimum effective concentration (MEC) of TMPyP for significant photodynamic activity was determined to be 0.8 μM under an irradiance of 314 ± 11 mW/cm