The design of fuel assemblies is in various ways associated with reactor physics, i. e., the science dealing with neutron chain reactions and nuclear fission. Reactor physics methods are incorporated in specialised computer codes that are able to deal with the geometry and the materials of a fuel assembly. So-called lattice codes (2D) treat a cross section of the assembly and solve the coupled space, energy, angle and time neutron transport problem. They also provide input to whole core calculation codes (3D) and fuel behaviour codes.

For the fuel, reactor physics has to address the effects of enrichment and possibly plutonium in the fuel, burnable absorbers, fuel burn-up (depletion) and the influence of control rods. For materials in an assembly, an important task is to evaluate the neutron fluence (time integrated neutron flux), which has an impact on mechanical properties and dimensional changes, for example growth and bowing in a neutron flux gradient.