Abstract: Photo-transmutation is an important path to handle long-lived fission products. In this research work, an optimization scheme of photo-transmutation induced by Laser WakeField Acceleration (LWFA) driven electrons is proposed. Numerical simulations of photo-transmutation of ¹³⁵Cs by this scheme are performed. Monte Carlo simulations show that with increasing electron energy, transmutation yield gradually saturates. The transmutation efficiency per unit electron energy has a peak near 40 MeV, with half-maximum energy of 20−120 MeV. To enhance electron charge within the half-maximum energy range and optimize transmutation yield, PIC simulation was used to study the transmission process of ultrashort and ultra-intense lasers in gas plasma. The results show that as plasma density decrease, the energy of electrons gradually increase while their charge are gradually reduced. Moreover, circularly polarized lasers exhibit higher electron energy and charge than linearly polarized ones. Through adjusting the plasma density and laser polarization, it is found that there is an optimal value for transmutation yield under the conditions of circular polarization and specific density. The scheme is expected to promote the studies of nuclide transmutation in a tabletop ultra-intense and ultra-short laser device with high repetition rate, as well as the potential applications in medicine and nuclear-waste management.