Officials said that an unmanned US aircraft fired two missiles on a house in the Shane Warsak area of Wana, the capital town of South Waziristan, killing four people and injuring three others.
The identities of the drone strike victims are not known yet.
On November 21, a similar aerial strike left at least four people dead and several others injured in South Waziristan.
Pakistani tribal regions are the target of US terror drones, with Washington claiming that its unmanned aircraft are targeting militants. However, casualty figures clearly indicate that Pakistani civilians are the main victims of the assaults.
The killing of Pakistani civilians, including women and children, in the airstrikes has strained relations between Islamabad and Washington.
The drone strikes have triggered massive anti-US demonstrations across Pakistan to condemn the United States violation of its sovereignty.