simulationism
Explanation
The Joke
The comic tackles the philosophical concept of simulationism -- the hypothesis that our reality might be a computer simulation run by a more advanced civilization. A character opens with: "I'm a religious simulationist. I believe we're in a simulation and therefore we should do things to amuse the simulators." Another character asks how they would do that.
The simulationist then lays out an ambitious program: they should create new exotic configurations of matter and energy, push computers to run ever more complex simulations, push the boundaries of human imagination, and make their corner of the simulated universe as complex and interesting as possible -- "because that should make us a fortune in a real universe." Essentially, they argue that if we are in a simulation, we should make ourselves entertaining enough that the simulators will not shut us down.
However, the final punchline deflates this grand vision. Someone asks: "How do you maintain interest in proton or quark-level interactions without the foundational understanding needed for leverage?" -- basically, how do you get people interested in the fundamental physics required for this project? The response is simply: "I dunno, it just seems like it would be cool for revenge" -- suggesting the entire elaborate philosophical framework was really just motivated by petty spite.
The Humor
The comic satirizes the simulation hypothesis by taking it to its logical extreme as a religion with practical imperatives. The humor escalates as the simulationist's program becomes increasingly grandiose and then collapses when confronted with a practical question. The final admission that it is all about "revenge" punctures the intellectual pretension, suggesting that even the most sophisticated philosophical positions often boil down to base human emotions. The hover text -- "Ironically, in this comic I'm reusing stock characters" -- adds a meta-layer, since reusing characters in a comic is itself a form of lazy simulation.
References
The simulation hypothesis was most famously formulated by philosopher Nick Bostrom in his 2003 paper "Are You Living in a Computer Simulation?" which argues that at least one of three propositions must be true: civilizations go extinct before becoming technologically mature, mature civilizations choose not to run simulations, or we are almost certainly living in a simulation.