In this paper, the author establishes the existence of positive entire solutions to a general class of semilinear poly-harmonic systems, which includes equations and systems of the weighted Hardy–Littlewood–Sobolev type. The novel method used implements the classical shooting method enhanced by topological degree theory. The key steps of the method are to first construct a target map which aims the shooting method and the non-degeneracy conditions guarantee the continuity of this map. With the continuity of the target map, a topological argument is used to show the existence of zeros of the target map. The existence of zeros of the map along with a non-existence theorem for the corresponding Navier boundary value problem imply the existence of positive solutions for the class of poly-harmonic systems.