Neo chooses the red pill because, as established by his behavior and Morpheus’s framing, he is driven to know what is wrong with his world and to live in alignment with that truth, even at the cost of comfort and safety. The scene is explicitly presented as a choice between continuing an illusory life—“believe whatever you want to believe”—and pursuing “the truth, nothing more,” and Neo has already risked his job, freedom, and safety in his obsessive search for the Matrix. The red pill is the concrete form of the answer he has been chasing; refusing it would mean willfully returning to a lie he can no longer ignore.
His stated dislike of fate and not being in control, and his escalating alienation as Thomas Anderson, reinforce that remaining in the Matrix would feel intolerable and disempowering. But these psychological factors mainly deepen, rather than displace, the core motivation: he wants to understand reality and escape the sense of wrongness that has been “like a splinter in [his] mind.” Later revelations about systemic control, trans allegory, and Gnostic symbolism enrich the significance of his choice, yet they operate mostly at thematic and structural levels, not as the conscious reasons Neo cites. Within the story as he experiences it, his choice is best explained as a deliberate commitment to truth and an authentic self over a comforting, prescribed illusion.
So the best-supported answer is that Neo chooses the red pill because, given who he already is by that point—an insomniac truth-seeker unable to accept a life he knows is wrong—taking the path toward truth is the only way he can live honestly with himself. Other frameworks (destiny, systemic control, trans and religious allegory) describe how that choice fits into larger patterns, but they supplement rather than replace this fundamental motivation.