Systems and methods for Virtual Network Function (VNF) service chain optimization include, responsive to a request, determining placement for one or more VNFs in a VNF service chain based on a lowest cost determination; configuring at least one programmable region of acceleration hardware for at least one VNF of the one or more VNFs; and activating the VNF service chain. The lowest cost determination can be based on a service chain cost model that assigns costs based on connectivity between switching elements and between hops between sites. The activating can include a Make-Before-Break (MBB) operation in a network to minimize service interruption of the VNF service chain.