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This comic refers to what we still call the "final frontiers" of human discovery: outer space, the oceans, the human mind, and Alaska. These places/regions have been only partially explored, or in Alaska's case, because it's called The Last Frontier.
The title text refers to the title of Star Trek V, titled Star Trek V: The Final Frontier. Randall (mis)interprets this title as Star Trek V the movie as one of the final frontiers, but since the film was released in 1989, he states that this frontier has probably been explored already. The phrase, "the final frontier," is used in the opening narration for the original Star Trek TV series:
Space: the final frontier. These are the voyages of the starship Enterprise. Its five-year mission: to explore strange new worlds. To seek out new life and new civilizations. To boldly go where no man has gone before!
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Most likely though of course not guaranteed reference for the title text is the recent stories out (about 2 days ago) saying that William Shatner regrets directing Star Trek V: The Final Frontier.
Quick example of one story here 
--WJBodin3 (talk) 21:17, 3 September 2018 (UTC)
- I would find the timing very suspicious at the very least. I think it's highly likely the news inspired this comic, especially in light of Star Trek being outright named - and specifically that instalment. NiceGuy1 (talk) 13:22, 4 September 2018 (UTC)
It is interesting that all the current frontiers seem somewhat equidistant from the "center" of the squarish figure, as if we have achieved the same level of knowledge/exploration in each category... Daiemos (talk) 15:18, 4 September 2018 (UTC)
- Each is on its own (unlabeled) axis, scaled to imply parity among the topics. See  126.96.36.199 16:53, 4 September 2018 (UTC)
- ...finished exploring it by now (Title text)
If Randall means space and not the movie alone this would contradict the comic itself where space is still a big challenge. --Dgbrt (talk) 16:24, 4 September 2018 (UTC)
- I was thinking that myself, he could be saying that star trek has been fully explored, which the could be a slight reference to the relatively hot topic about star trek discovery. Some trekkies lamenting the fact that they didn't want another prequel... If on the other hand it is a reference to space itself, randall could have left the contradiction in on purpose, as part of the joke. 188.8.131.52 18:02, 4 September 2018 (UTC) Sam
- Actually the title text states that the movie is only a small part of the space frontier and also probably fully explored by now. So the diagram is about Space, not the movie.184.108.40.206 04:39, 5 September 2018 (UTC)
I, embarrassingly, thought it referred to "Looking for Alaska." I am not worthy of XKCDhood
220.127.116.11 00:36, 13 November 2018 (UTC)
I always assumed that the final frontier to which the title was referring was "Death". Brenda (talk) 09:28, 25 January 2020 (UTC)