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Isotopes are alternate forms of an element which contain the same number of Protons but a different number of Neutrons. As a result, isotopes have different chemical and physical properties. Isotopes can be recognised by the number in their name. E.g. Uranium-233, Uranium-235 and Uranium-238. There are 24 different isotopes represented in NuclearCraft plus an Oxide of each isotope.

Isotopes are produced in the Isotope Separator, Decay Hastener and Fuel Reprocessor. They come in items and tiny clumps. Nine tiny clumps can be combined into a regular item of that isotope. E.g. an ingot of Uranium placed in an Isotope Separator will produce 2 items of Uranium-238 and 2 tiny clumps of Uranium-235.

Isotopes are used in the creation of Fuel for the Fission Reactor. For information on the differences in isotopes, see the article on Fission Fuels.