This study presents urease-powered nanobots for radionuclide therapy of bladder cancer. The nanobots, based on mesoporous silica nanoparticles (MSNPs), are powered by urease and can self-propel in the presence of urea. They were radiolabelled with ¹³¹I and tested in an orthotopic mouse model of bladder cancer. In vivo and ex vivo imaging showed enhanced accumulation of the nanobots at the tumour site, with an eightfold increase in uptake detected by positron emission tomography (PET). Ex vivo optical contrast imaging confirmed tumour penetration by the nanobots. Intravesical administration of ¹³¹I-labeled nanobots resulted in a 90% reduction in tumour size, demonstrating their effectiveness as delivery systems for radionuclide therapy (RNT). The nanobots' active motion enabled efficient tumour accumulation at doses much lower than those required for passive particles. The study highlights the potential of urease-powered nanobots as a promising alternative to traditional treatments for bladder cancer, offering improved therapeutic efficacy and reduced side effects. The results suggest that these nanobots could be translated into clinical applications for bladder cancer therapy.This study presents urease-powered nanobots for radionuclide therapy of bladder cancer. The nanobots, based on mesoporous silica nanoparticles (MSNPs), are powered by urease and can self-propel in the presence of urea. They were radiolabelled with ¹³¹I and tested in an orthotopic mouse model of bladder cancer. In vivo and ex vivo imaging showed enhanced accumulation of the nanobots at the tumour site, with an eightfold increase in uptake detected by positron emission tomography (PET). Ex vivo optical contrast imaging confirmed tumour penetration by the nanobots. Intravesical administration of ¹³¹I-labeled nanobots resulted in a 90% reduction in tumour size, demonstrating their effectiveness as delivery systems for radionuclide therapy (RNT). The nanobots' active motion enabled efficient tumour accumulation at doses much lower than those required for passive particles. The study highlights the potential of urease-powered nanobots as a promising alternative to traditional treatments for bladder cancer, offering improved therapeutic efficacy and reduced side effects. The results suggest that these nanobots could be translated into clinical applications for bladder cancer therapy.