Superconducting gamma-ray detectors offer an order of magnitude higher energy resolution than conventional high-purity germanium detectors. This can significantly increase the precision of non-destructive isotope analysis for nuclear samples where line overlap affects the errors of the measurement. We have developed gamma-detectors based on superconducting molybdenum-copper sensors and bulk tin absorbers for nuclear science and national security applications. They have, depending on design, an energy resolution between ∼50 and ∼150 eV FWHM at ∼100 keV. Here, we apply this detector technology to the measurement of uranium isotope ratios, and discuss the trade-offs between energy resolution and quantum efficiency involved in detector design.