The duplex pellets under a “Low-Interact” (LOWI) nuclear fuel design, which consist of an outer enriched annulus and a depleted or natural core, can provide lower center temperature and reduced probability of pellet-clad mechanical interact (PCMI). Analysis and experiments were done in 1970s to examine the benefits and cost of LOWI design for water-cooled reactors. Results showed that the additional economic cost of this design should not be neglected in spite of the benefits. However, due to the improvement of nuclear fuel fabrication technology in the past 30 years, the benefits of LOWI design become more significant, especially when the potential of other methods to elevate the power density and overcome the constraints on ramp rates in power reactors is running out. In order to evaluate the feasibility of deploying the LOWI fuel in commercial and research reactors, neutronics and thermal calculations are made to figure out the performance of duplex UO2 pellets in particular reactors. It is shown that the center temperature of pellet has been greatly reduced without any change on assembly and core geometry, which means the opportunity of less fission gas production, higher power density and more adequate safety margin. A mechanical analysis of a typical LOWI design is also done. The challenges on duplex pellet manufacture are also discussed. Several fabrication techniques are presented to show the potential of cutting the cost of pellet production.