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Explanation
The Joke
A woman questions why physics should work differently at various scales of measurement, saying it makes no sense. The man responds with a kind of resigned acceptance: "Look man, I dunno. Maybe we can't know. All we can do is try to see what's going on, understand what we can, and write it down for future people." The bottom caption then reframes this entire exchange with the punchline: "What if science is just humans adding comments to sloppy code?"
The comic takes the genuine mystery of why the laws of physics seem to behave differently at quantum scales versus macroscopic scales and reframes the entire scientific enterprise as something analogous to software maintenance. The universe is the "sloppy code" (written by God, nature, or whoever), and scientists are merely the hapless programmers trying to make sense of it and leaving comments (papers, theories) for the next person who has to deal with it.
The Humor
The joke works on multiple levels. First, it captures a real frustration in physics: quantum mechanics and general relativity do not play nicely together, and nobody fully understands why. Second, the metaphor of "commenting sloppy code" is immediately relatable to anyone who has worked in software development, where you often inherit incomprehensible code and can only document your best understanding of what it does. The hovertext deepens the joke further by suggesting that if we look deep enough into the digits of pi, we might find God's own TODO comments about fixing quantum gravity later -- the ultimate version of a developer leaving a note to fix something "in a future release."
References
The comic references the well-known tension between quantum mechanics and general relativity, sometimes called the problem of quantum gravity. The hovertext alludes to pi (a fundamental mathematical constant) and the speculative idea that hidden messages might be encoded in its digits, a concept explored in Carl Sagan's novel Contact.