As the Memphis Music Hall of Fame explains, Gangsta Boo (pictured) left Three 6 Mafia in 2000 to pursue solo projects. Boo released a number of records under her stage name both before and after her departure from the group (via AllMusic). At that time, Boo was briefly replaced in the lineup with Chastity "La Chat" Daniels. On Three 6 Mafia's last full-length, "Laws of Power," only Juicy J and DJ Paul, who were also co-founders of the Hypnotize Minds record label, remained in the lineup. That same year, Three 6 Mafia was inducted into the Memphis Music Hall of Fame, according to Complex.

Also in 2012, Juicy J produced hits on his own, like "Bandz a Make Her Dance" with rappers Lil Wayne and 2 Chainz. J stayed active as a solo artist both before and after Three 6 Mafia went on hiatus. His last full-length under his own name, "Stoner's Night," came out in 2022. With the Mafia on a break, DJ Paul also diversified his business interests with DJ Paul's BBQ Rub and Sauce, via that product's website. In 2015, Koopsta Knicca, who at that time had also gone solo, died at the age of 40 in Memphis from what was reported as a massive stroke, according to Rolling Stone. Lord Infamous, also a solo artist, died in 2013 from a heart attack at the age of 40, also per Rolling Stone.