The card illustrations and flavor throughout the game is based on the Cthulhu universe, with a humorous slant. The goal of the game is to reduce your opponent's sanity (i.e. life total) to zero. There are various entities (many with tentacles), artifacts, and locations to use to accomplish this goal.
I really enjoyed the single-player introductory campaign in Cthulhu Realms. In addition to teaching you the basics of how to play, the campaign tells a hilarious story of a hapless IRS auditor (you) who stumbles into a web of cultists and entities from beyond. The first chapter in particular is well worth playing through just to read the mission briefings.
Despite the similarities, Star Realms and Cthulhu Realms play quite a bit differently. One major difference is the ability that a few cards have to bring back a card that you've "abjured" (removed from your deck or the center row) and put it on top of your deck. That can be a very powerful option to obtain an extra card or re-use a good card's abilities. Another difference is that there are only three factions (Star Realms has four), and several cards take advantage of effects from other faction effects. I'm still getting used to the differences, but it's pretty clear already that playing Cthulhu Realms requires some different strategy than Star Realms.
I recommend that anyone who likes the deck-building genre take a look at Cthulhu Realms. Certainly go through the campaign, which is worthwhile just for the story. You may find that the insanity appeals to you.