The song features guest vocals from Ma$e and Sean "Puff Daddy" Combs. The instrumental contains a sample of the Diana Ross song "I'm Coming Out", including backing vocals of "I'm, coming, out". The refrain of the song was sung by Kelly Price. Based on airplay and chart success the song is considered one of the most popular singles in hip hop history. It remains a radio favorite to this day.
"Mo Money Mo Problems" was able to top the Billboard Hot 100 for two weeks giving Biggie his second number 1 hit in the US. The song hit number 1 after he had died. It was preceded by "I'll Be Missing You" by Puff Daddy featuring 112 and Faith Evans (meaning that Puff Daddy spent 13 weeks in a row at the top of the Hot 100) and was succeeded by "Honey" by Mariah Carey. The single reached #6 in the UK charts.