A detailed theoretical study has been made of Pt–Pd nanoalloy clusters, with the interatomic interactions modelled by the Gupta many-body potential. For 18–20 atom clusters, a genetic algorithm has been used to find the lowest energy structures for each size and for all possible compositions. A number of different structure motifs have been identified, with the structure often depending critically on cluster composition. Our general finding, which is in agreement with our previous theoretical study, and with experimental results, is that in the lowest energy isomers (“homotops”), the Pd atoms lie predominantly on the surface of the cluster, with the Pt atoms mainly occupying interior (core) sites. For some specific sizes and compositions (PtPd₁₈ and Pt₁₂Pd₁₂) the structures and degree of atomic segregation of the most stable geometrical and permutational isomers (“homotops”) have been rationalized by analysis of partial (individual atomic) binding energies, distribution-dependent structural order parameters, atomic coordination and the number of Pt–Pt, Pt–Pd, and Pd–Pd bonds. These approaches have also been used to explain the lowest energy structures obtained by doping single Pt or Pd atoms into 1–3-shell icosahedral clusters of the other element. The observed lowest energy homotops found by the genetic algorithm for a number of 2-shell icosahedral 55 atom clusters (of varying compositions) have also been rationalised and a study of alternative, cuboctahedral geometries has been made. Finally, a number of factors have been identified which are important in determining isomer (including homotop) stability for Pt–Pd nanoalloys.