The CIA-operated spy plane fired two missiles at the house near Miranshah, the main town of North Waziristan Agency, which has been described by US officials as a stronghold of Taliban and al Qaeda elements.
Security officials and local residents were quoted by the media as saying that four suspected militants were killed in the attack.
The identity of those killed could not immediately be ascertained.
The house caught fire after being hit by the missiles and militants cordoned off the site and prevented people from approaching the area.
On May 23, four suspected militants were killed in a drone strike near Miranshah, while 10 suspected militants were killed in a missile attack in the same region the following day.
The string of drone strikes have added to tensions between the US and Pakistan, which has been calling for an end to the attacks.
The strikes came days after President Asif Ali Zardari left the NATO Summit in Chicago without announcing any move to reopen supply lines for foreign forces in Afghanistan.
Pakistan closed the supply routes after a cross-border NATO air strike from Afghanistan killed 24 of its soldiers in November.
Since then, Islamabad has been insisting that Washington halt the drone strikes, which Pakistani leaders have described as a violation of the country’s sovereignty and international law.
The US has been pressing Pakistan to launch a military operation in North Waziristan agency, which American officials have said is a safe haven for the Haqqani network that has been blamed for a series of brazen attacks on Western targets in Afghanistan.