The results of complex simulations using PIC-GEANT4 (particle-in-cell and Monte-Carlo) codes based on the generation of a high-energy electron bunch by a short laser pulse propagating in a relativistic self-trapping regime in a near-critical plasma has been applied to assess the possibility of medical isotope production and nuclear waste transmutation. It has been demonstrated that a 10 Hz 30 fs 4 J laser pulse is well suited to the production of therapeutic amounts of several standard medical radionuclides (111In, 123I, 103Pd, 62Cu, 64Cu). The use of direct electron irradiation has an advantage over the use of bremsstrahlung gamma radiation from the converter due to the simplification of the production scheme without loss of radionuclide yield. The study of the transmutation of long-lived fusion products showed low efficiency and the need for preliminary isotope separation. Achieving as little as 10% reduction in the activity of a 10 g sample requires the continuous operation of the next-generation laser system at a high repetition rate (1 MHz–100 kHz) for (one to ten) years.