The attack was the second in two days in North Waziristan, considered by US officials to be the most dangerous place in the world where al-Qaeda fighters are plotting attacks on the West.
The missile slammed into a compound used by anti-government fighters in Palooseen, a village located in the district of Mir Ali, Pakistani officials said.
Also on Friday, at least three police officers were killed after a roadside bomb hit their convoy in the northwestern Pakistani city of Peshawar, police said.
Officials said about six people were also wounded when their vehicle drove over a bomb buried beneath a road.
The attack, shortly after midnight, came hours after a suicide bomber blew himself up outside a court building in the city, killing at least 19 people.
"It was a remote-controlled bomb. Two policemen died on the spot, while a third has succumbed to his injuries a short while ago," Mohammad Haroon, a police official, told the Reuters news agency.
'Operational functioning'
During his second visit to Pakistan since taking office this year, Panetta held talks with Yousuf Raza Gilani, the prime minister of Pakistan, on Washington's policy review in Afghanistan.
A statement released by Gilani's office said that both agreed on "operational functioning between the two militaries and intelligence agencies" to eliminate the terror threat.
Peshawar, capital of the North West Frontier Province (NWFP) bordering Afghanistan, has borne the brunt of the attacks perpetrated by the Taliban in recent weeks in retaliation for a military offensive launched in the country's semi-autonomous tribal region of South Waziristan.
The Pakistani military launched its offensive against members of the Tehreek-e-Taliban Pakistan, one of the main anti-government groups, nearly a month ago, pitting about 30,000 troops against an estimated 10 to 12,000 Taliban fighters in South Waziristan.
Eight suicide bomb attacks in Pakistan this month alone - six of them in Peshawar - have killed 110 people.
The Pakistani Taliban has claimed responsibility for several of the attacks, but Gilani said that many of the group's commanders were on the run.
"They are using the weapons they have scattered here and there," he said.
"God willing, it will take some time, but I assure you things will return to normal soon."
The US, weighing options for how to tackle an intensifying Taliban campaign in Afghanistan, has welcomed the offensive but is keen to see Pakistan tackle Afghan Taliban factions based along the border.
Despite the barrage of bombs, the Pakistani government says it is determined to defeat the Taliban fighters with the help of its allies.