Why? That's the question.
There's only so much money people are prepared to spend on publicity stunts (which is what the Manned Program really is, as much as I love it).
So, you need to have some over-riding reason. Discovering an alien base on the moon might work. Discovering an alien civilization on Mars would work. Having nuggets of unobtainium lying around on the surface of the moon might work, if unobtainium actually had any use. Solar Power Sats from Lunar resources might work IF everything went perfectly....
O'Neill's L5 colony, with Lunar resources and SPSs was a serious stab at providing a rationale, but the design was iffy, as were the economics.
Europeans settled the New World mostly because the cost/benefit ratio was so good. Individuals could pay passage and get cheap land (for North America), or nations could send a handful of men and get access to LOTS of gold and silver (Spain).
There's no free land for agriculture in space, and even if gold nuggets were common on the surface of the moon, it probably would be too expensive to mine the stuff with current tech. And a proper cheap space transportation system would require a market first.
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OK, DotCom bubble lasts a little longer. Kistler actually gets their financing lined up (that's probably 2 independent PoDs). The K-1 works as advertised (ha, ha), or at least can be made to work vaguely somewhat like advertised (that might be possible). You now have affordable access to space, sort of.
New markets develop. More reusable launchers are built. Lockheed turns the VentureStar into a TSTO and it's vaguely affordable; Boeing resurrects the DC-Clipper, as a first stage of a TSTO (probably won't work as an SSTO affordably).
That gets lots of stuff into Earth orbit (LEO, MEO, GEO). It still doesn't get a moon base.
But maybe it makes lunar exploitation of lunar resources feasible. Firstly for oxygen (oxygen in LH/Lox engines is most of the mass), then maybe for metals for space construction.
Again, exploitation of near earth asteroids, especially for earth orbit infrastructure, might be feasible, IF we first get that cheap(ish) access to space. Carbon for lifesupport, iron for structural stuff. Maybe hydrogen.