Aspects of the present disclosure relate to connection blocks and pump manifold systems, and related methods, for pumping operations (such as frac operations). In one implementation, a connection block for disposition along a pump manifold of a pump system includes a first end hub having a first tube and a first outer shoulder extending outwardly relative to the first tube. The connection block includes a second end hub opposing the first end hub. The second end hub has a second tube and a second outer shoulder extending outwardly relative to the second tube. The connection block includes one or more faces between the first end hub and the second end hub.