Origin. The scene opens the game, released on 26 October 2004: corrupt police officers dump CJ in rival territory, and he sighs the line. It barely circulated until a YouTube upload on 7 January 2015, became a reaction image later that year and peaked in April 2019 with green-screen edits. Know Your Meme's entry has more than 1.1 million views.
How people use it. CJ's face goes over any cyclical disaster: exams, patch notes, a new delay. Rockstar itself recreated the scene for the remastered trilogy in November 2021 (PC Gamer).
Example. CJ's tired look over the caption "when the winter holidays end and the second semester begins".