The album contains 14 tracks and includes guest appearances from Roddy Ricch, Doja Cat, Gunna, Fleet Foxes, the Kid Laroi, and the Weeknd.

[4][5] On July 21, 2020, Malone was interviewed by The Wall Street Journal, in which he said: To be honest, I think everyone in America is going a little bit crazy sitting at home all day.

He felt that the songs on the album "speak more to how I'm feeling at the moment: the ups and downs and the disarray and the bipolar aspect of being an artist in the mainstream".

American record producer Louis Bell, a close friend and frequent collaborator of Malone, felt that it blends "molten lava and fire" and "cyan blues and whites".

[14] On May 14, 2022, he appeared as a musical guest on Saturday Night Live and performed "Cooped Up" with Roddy Ricch, as well as "Love/Hate Letter to Alcohol", joined by Fleet Foxes.

[32] Rhian Daly from NME enjoyed the album, saying, "The occasional outdated attitude and some light filler material here and there aside, Twelve Carat Toothache is another step up for Post Malone.

[39] Writing for The Daily Telegraph, Kathleen Johnston stated, "Despite what the polished sonics might suggest, Twelve Carat Toothache is an ambitious record with real range, proving that Post has found his groove as America's kaleidoscopic king of new-era pop".

[1] Jon Caramanica of The New York Times praised the album, stating, "Some of Post Malone's brightest sounds to date: "Wrapped Around Your Finger" has 1950s sweetness and 1980s syntheticness, and "I Cannot Be (a Sadder Song)" has a bubbly undertow that recalls some of the squeakiest K-pop.

[42] In a positive review, Variety's Chris Willman said, "Twelve Carat Toothache finally feels like a transitional album for one of pop's biggest stars.

But with no small help from Bell, who's the best kind of musical enabler, Malone's turns of melodic phrase and aptitude for true confessions are making him a far more interesting artist than we could have guessed even a couple of albums ago".

[43] AllMusic's Neil Z. Yeung wrote, "While the rap-preferring fans will still gravitate to his first two efforts, listeners with an appreciative ear for his genre-sampling maturation into the mainstream will find Twelve Carat Toothache to be a fascinating emotional exploration of a conflicted artist who can't help but churn out star-making hits at the expense of his own happiness".

[34] Maura Johnston of Rolling Stone said, "His fourth album is full of big-name cameos, sweeping gestures, and pensive vibes".

[41] In his review, Matthew Strauss of Pitchfork states, "Post Malone's fourth studio album is slick, streamlined, and a little less vulgar and ostentatious than his earlier work—a sign that he's taking himself more seriously, for better or worse".

[35] In a mixed review, Clash's Robin Murray stated, "Neither one thing or another, the lack of definition on the project results in something quietly rebellious, but curiously unsatisfying".

[36] Mackenzie Cummings-Grady of HipHopDX said, "Lukewarm contributions from Doja Cat, the Kid Laroi, Roddy Ricch and others can't help Post Malone get out of the quicksand.