Discussing and researching issues related to their safety is essential to guarantee the continuity of fission systems in generating energy for existing and new electrical matrices. Commercial fission reactors currently in operation have undergone a series of redesigns. One aspect much discussed in recent years is related to research about new fuels and cladding materials. Therefore, in this work, the feasibility of replacing Zircaloy-4 with FeCrAl-based alloys (C06M, C35M, C36M, Kanthal APMT) was evaluated considering these materials' physical–chemical, thermal, and neutronic properties. Moreover, thermal–hydraulic and neutronic simulations have been presented to compare the cladding behavior in a PWR core in steady state and transient operation conditions. The results showed, in a general way, that the analyzed alloys have equivalent properties from a physical–chemical and thermal point of view. Despite the similarity, the Kanthal APMT alloy presented the worst performance, and the C35M alloy showed more advantageous characteristics. Considering the similarities in the composition of the C06M, C35M, and C36M alloys, which have the same elements in their constitution, the alloy with the best thermal performance has the lowest aluminum content. Considering the neutronic behavior, the Kanthal APMT alloy, with more Cr percentile, presents the lowest neutron effective multiplication factor, keff. Axial and radial power distribution did not change significantly after the cladding replacement. Nevertheless, modifications must be made to keep the criticality during the fuel cycle burnup for all FeCrAl alloys.