After numerous talks with Death Row Records CEO Suge Knight, Lopes severed her solo deal with Arista (despite remaining signed to the label as a member of TLC) and signed with Knight's Death Row Records in January 2002, intending to record a second solo album under the pseudonym "N.I.N.A." (New Identity Not Applicable). She was recording with David Bowie for the project, whom she was also trying to get involved with the fourth TLC album. The project was also to include several songs recorded with Ray J along with close friend Missy Elliott. After Lopes' death in April 2002, Death Row Records still had plans to complete and release the album (unfinished at the time of Lopes' death) in October 2002, but the album was cancelled for unknown reasons. In 2011, some tracks from the album were uploaded onto YouTube featuring artists from Tha Row Records. Lopes's unreleased songs were also sampled by TLC for their fourth album 3D after she died. Another track, "Too Street 4 T.V" (featuring Danny Boy), was released on the soundtrack to the 2003 film Dysfunktional Family.
On April 25, 2002, Lopes was driving a rented Mitsubishi Montero SUV in La Ceiba, Honduras, when she swerved slightly to avoid a truck (it is not clear if the truck was slow-moving or stationary) then immediately to the right as she tried to avoid an oncoming car. The vehicle rolled several times after hitting two trees, throwing Lopes and three others out of the windows, and finally coming to rest in a ditch at the side of the road. Lopes, at the age of 30, died instantly of "fracture of the base of the cranium" and "open cerebral trauma", and was the only person fatally injured in the accident. A cameraman in the front passenger seat was videotaping at the time, so the last seconds leading up to the swerve that resulted in the fatal accident were recorded on video. Her sister Reigndrop Lopes was in the vehicle and survived the collision.
Lopes' funeral was held at New Birth Missionary Baptist Church in Lithonia, Georgia, on May 2, 2002. Thousands of people attended. Engraved upon her casket were the lyrics to her portion of "Waterfalls", stating "Dreams are hopeless aspirations, in hopes of coming true, believe in yourself, the rest is up to me and you." Gospel duo Mary Mary sang their song "Shackles (Praise You)" at the funeral. Lopes was buried at Hillandale Memorial Gardens in Lithonia.