The things we don't know, but will know thanks to successfuly exploited wealth, are larger than what we will know otherwise... For now the first order is to reduce the cost of access to space. That's the foremost barrier. Other things such as going to mars or NEOs are already feasible by optimization approaches (of current hardware) such as slow boost of lots of hardware (for TMI) to EDO by ion propulsion a long while ahead of the actual manned transport(s).. Then it's a matter of dealing with the worst problems like solar radiation and excessively fast NEO rotation. Those are probably cheaper and simpler to resolve.