soulmate-4
Explanation
This comic takes the romantic concept of a "soulmate" and subjects it to God's brutally literal interpretation.
A person prays to God asking, "Dear God, is there a soulmate out there for me somewhere?" God replies, "That depends." He then asks a clarifying question: does the person mean a soulmate in the sense of "an intangible connection of spirits" where they will "feel whole and complete and fulfilled" -- or a soulmate in the sense of "a person who is so perfectly matched with all of your personality traits, quirks, and preferences that being together will reveal you are experiencing nothing."
In other words, God is distinguishing between the idealized romantic notion of a soulmate (someone who completes you) and a more logically rigorous version (someone so identical to you that there is zero friction, zero surprise, and therefore zero experience -- a kind of emotional nullification). The first sounds wonderful; the second sounds like an existential void.
The person hesitantly starts to say "the second kind," at which point God reminds them: "Remember, I can read your thoughts" -- and adds, "with a huge axe." The implication is that God knows the person actually wants the impossible romantic version, and is threatening them for even pretending otherwise.
The humor lies in the philosophical deconstruction of the soulmate concept. The idea that a truly perfect match would result in "experiencing nothing" is a clever reductio ad absurdum -- if someone agrees with you on literally everything and matches your every trait, the relationship would be featureless and empty. The joke also plays on the common SMBC trope of God being exasperated, omniscient, and mildly threatening.