This study presents a cross-disciplinary reactor-to-repository framework to compare different advanced reactors with respect to their spent nuclear fuel (SNF). The framework consists of (1) OpenMC for simulating neutronics, fuel depletion, and radioactive decays; (2) NWPY for computing the repository footprint for SNF disposal given the thermal constraints; and (3) PFLOTRAN for simulating radionuclide transport in the geosphere to compute the peak dose rate, which is used to quantify the repository performance and environmental impact. We first perform the meta-analysis of past comparative analyses to identify the factors led previously to inconsistent conclusions. We then demonstrate the new framework by comparing five reactor types. Significant findings are that (1) the repository footprint is neither linearly related to SNF volume nor to decay heat, due to the repository’s thermal constraint, (2) fast reactors have significantly higher I-129 inventory, which is often the primarily dose contributor from repositories, and (3) the repository performance primarily depends on the waste forms. The TRISO-based reactors, in particular, have significantly higher SNF volumes, but result in smaller repository footprints and lower peak dose rates. Our analysis highlights the diversity of these reactors, each of which should be evaluated individually. The open-source framework ensures proper cross-disciplinary connections between reactor simulations and environmental assessments, as well as the transparency/traceability required for such comparative analyses. It aims to support reactor designers, repository developers and policy makers in evaluating the impact of different reactor designs, with the ultimate goal of improving the sustainability of nuclear energy systems.