Motivated by this findings, herein, we evaluate by means of density functional theory (DFT) the stability, CO poisoning resistance and HOR/ORR activity of small-size pure Pt and alloy PtGe clusters supported on a variety of 2D supports, viz., pentagon-octagon-pentagon reconstructed divacancy graphene (5-8-5-DV), boron-doped graphene (gr-B), phosphorene, silicene, germanene, 2H-MoS2 and SmSI. In the initial step, we carry out a global minima search to locate the most stable structures. Afterwards, we investigate their structural and energetic properties and compute the Gibbs free energy diagrams for the HOR and ORR mechanisms. Our aim is to simultaneously understand the interplay between promoter and support by carrying out a thorough systematic study. Alloying and MSI effects work in two directions. On the one hand, the support increases the stability and changes the electronic structure of the cluster via MSI. On the other hand, the cluster can change the electrical properties and catalytic activity of the support, which can be modulated with its size and composition. Hence, the best of both cluster and support can be obtained with an efficient MSI. In addition, Ge is chosen to introduce a dual adsorption site for the ORR intermediates and improve the energetic efficiency (reduced overpotential). The present study may inspire helpful guidance for the pursuit of new Pt-based electrocatalysts resilient to CO poisoning with ultra-low loading of precious Pt.