We investigate the shock response of Ni + Al reactive nanoparticle systems through molecular dynamics simulations. The powder configurations with varying arrangements and densities are constructed by stacking equal-sized Ni and Al particles based on five typical crystal structures, i.e., zinc-blende, NaCl, CsCl, AuCu and the close-packed. The effects of configuration and shock strength on mechanochemical and diffusion processes in the shock-induced chemical reactions are characterized. A reaction kinetic model is developed to describe these behaviors, assess the extent of mechanochemical effect, and explain the occurrence of ultra-fast reaction. Significant dependence of shock wave velocity, plastic deformation, temperature response, chemistry and microstructure change on particle packing and density is observed under shock loading at the same piston velocity, but we see a relatively weak dependency on the stacking mode with the same density. Our results indicate the important role of particle coordination number and density in shock response of energetic powder materials.