There’s some interesting possibilities that hold some traction. The best shot I think we have is a laser pointed at a black hole, binary star pair, pulsar, or other fast rotating celestial body. In essence, we shot the laser in an orbit around said body and the laser loops back around to us with slightly more energy than it left with. Essentially an energy scoop if you will. That solves propulsion and potentially energy issues.

As far as the human resource goes, we most likely would need to construct generational ships. You’re right space is VAST and even with light-speed still takes large amounts of time to traverse. A generation ship helps alleviate this. Just basically a subset of our brightest and most talented minds living their life floating through space with the children being the pioneers of new frontiers. We also could potentially use cryogenics, although that leaves a lot more room for error and entire missions could potentially be lost over one glitch in the system.

I think our biggest hurdle at the moment is any one of these missions is going to require a vast amount of resources and are going to take the cooperation of all nations, something that unfortunately, doesn’t seem to be happening anytime soon.