The more I study human spaceflight, the more clear it’s becoming that even going to Mars has a huge number of known risks, to say nothing of the unknown unknowns. Space agencies are necessarily risk-adverse, which makes me wonder whether we’ll ever see interplanetary missions. (Given the expenses involved, I don’t see the private sector being able to make this work for several more decades.) We may not just be trapped in the inner Solar System, but trapped in the Earth-Luna gravity well, for a long time to come.
If I were going to plot a way out, it looks something like this: first, we develop reusable launch vehicle technology and get back to Luna. If we have to stick with the Senate Launch System, so be it; we can always switch to better launch vehicles later. Developing Gateway and lunar surface operations does at lot to test our assumptions about life in deep space, and develop the technology to do it safely.
Once we’ve gotten back to Luna, it might be possible to develop an economic presence there. It’s easier to get to LEO from Luna than Cape Canaveral, so areas like in-space refueling (for satellites, at first) and on-orbit manufacturing might be able to jumpstart that sector. It won’t happen overnight, and will start out primarily robotic, but we can build an off-world economy that way.
For human space exploration, we move on to near-Earth asteroid rendezvous. This is ambitious, but a lot less ambitious than a Mars mission. You don’t need heavy landers, and don’t need nearly as much Delta V. There’s also a greater degree of flexibility if you aren’t going as far out. We could conceivably cut that sort of mission short if the astronauts develop medical problems, in a way that we couldn’t if they’re en route to Mars following a Hohmann transfer orbit. You’re less likely to need to do that, though, because the overall duration is a lot lower. With the right planning, we might be able to cut the transfer periods down to just a month or two.
The big thing, for Mars and beyond, is developing better propulsion systems that enable higher-energy transits and massier spacecraft. Radiation shielding will be massive, even if we manage to cook up some sort of active scheme with magnetic fields, and the ideal way to deal with weightlessness is to build a spinning spacecraft. Currently, the mass ratios don’t work out for that.
Space agencies (and regulators!) are, again, risk averse, so I don’t see that investment happening in the near term. Rather, I think the real place that we see the development of VASIMR or nuclear thermal rockets to TRL 9 is with cargo in the Earth-Luna system. The goal won’t be high-energy trajectories, but rather efficient propulsion for getting up from and down to LEO. Probably up, mostly; we can use a combination of mass drivers and aerobraking when transporting non-delicate cargo down from Luna. Once there’s a market there, I could really see the private sector investing in advanced propulsion, and from there, opening up the Solar System.