About 30 people have now died in five attacks on Shis claimed by the Pakistani Taliban over the past five days while about 100 were wounded in the run-up to the Ashoura holiday, which commemorates the 7th-century death of the Prophet Muhammad's grandson.
The schism between Sunni and Shia Muslims dates back to that time.
Sunday's explosion went off as hundreds of Shias were passing through the main intersection of the city of Dera Ismail Khan.
An initial investigation suggested a bomb was planted near a shop along the procession route, and city police chief Sohail Khalid said: "The bomb contained about eight kilograms of explosives and steel balls, and was detonated with a remote control device."
Several of the injured are in a serious condition, according to local hospital official Faridullah Mahsud, who added that three members of a paramilitary unit providing security were among the injured. Dr Mahsud confirmed the five deaths.
Qais Abbas, a Shia survivor, said the procession was in the Chogla area of the city when the bomb went off.
One of his relatives was in a critical condition, he said, but he and others were moving the wounded to other hospitals that were better equipped.
"Here, we are not getting proper care for them, there are not enough doctors or medicines," he said.
The same city was hit by a similar bombing on Saturday, which killed seven and injured 30.