The missiles hit a vehicle and a compound in Dargah Mandi village in North Waziristan, around 10 kilometres (six miles) west of the main town of Miranshah in an area considered a stronghold for the Al-Qaeda-linked Haqqani network.
"Four of them were Uzbeks and two were Punjabi Taliban," said an intelligence official in Miranshah referring to militants from Pakistan's central Punjab province who have taken shelter in North Waziristan.
Officials said militants had parked their pick-up truck against the outer wall of the compound.
"Both compound and truck were completely destroyed. Local informers told us that both are still on fire," he said.
Another senior security official confirmed the strike and said the death toll could rise.
The strike came as Pakistani Taliban and the Islamic Movement of Uzbekistan said that Uzbek militants had been deployed in a siege of the country's busiest airport that began Sunday night and ended late Monday morning, killing 37 people including the 10 attackers.
That attack shredded a tentative piece process that began earlier this year with the Tehreek-e-Taliban Pakistan (TTP), who rose up against the state in 2007 in an insurgency that has claimed thousands of lives.
It also raised serious questions about how militants could strike at the airport serving Pakistan's economic hub, concerns which were underscored by a follow-up attack at an airport checkpoint the next day in which two Taliban gunmen escaped without causing casualties.
Around 60,000 residents have fled North Waziristan, which is one of seven tribal districts along the Pakistan-Afghanistan border, since late May fearing a long-awaited ground offensive could be imminent.
Pakistan has so far reacted with air strikes in the Tirah Valley of the Khyber tribal district which lies further to the north, killing at least 25 people on Tuesday.
The United States had offered its assistance in investigating the siege, though it is not yet clear whether Pakistan accepted the offer.
"The United States condemns the attack on the Karachi airport. And our hearts go out... to the families of the victims and those who were wounded in that attack," said White House spokesman Josh Earnest Monday.
More than 2,000 people have been killed in drone attacks since August 2008 according to an AFP tally, with critics charging that the strikes cause many civilian casualties.
The last drone attack on Pakistani soil occurred on December 25, 2013, killing three suspected militants. According to media reports the strikes had been temporarily halted at the Pakistani government's request.