Disposal of long-lived fission products (LLFPs) produced in reactors has been paid a lot attention for sustainable and clean nuclear energy. Although a few transmutation means have been proposed to address this issue, there are still scientific and/or engineering challenges to achieve efficient transmutation of LLFPs. In this study, we propose a novel concept of advanced nuclear energy system (ANES) for transmuting LLFPs efficiently without isotopic separation. The ANES comprises intense photoneutron source (PNS) and subcritical reactor, which consist of lead–bismuth (Pb-Bi) layer, beryllium (Be) layer, and fuel, LLFPs and shield assemblies. The PNS is produced by bombarding radioactive cesium and iodine target with a laser-Compton scattering (LCS) γ-ray beam. We investigate the effect of the ANES system layout on transmutation efficiency by Monte Carlo simulations. It is found that a proper combination of the Pb-Bi layer and the Be layer can increase the utilization efficiency of the PNS by a factor of ~ 10, which helps to decrease by almost the same factor the LCS γ-beam intensity required for driving the ANES. Supposing that the ANES operates over 20 years at a normal thermal power of 500 MWt, five LLFPs including ⁹⁹Tc, ¹²⁹I, ¹⁰⁷Pd, ¹³⁷Cs and ⁷⁹Se could be transmuted by more than 30%. Their effective half-lives thus decrease drastically from ~ 10⁶ to less than 10² years. It is suggested that this successful implementation of the ANES paves the avenue towards practical transmutation of LLFPs without isotopic separation.