The unmanned aircraft fired two missiles at a vehicle when it entered a madrassa near the house of Militant Commander Ainullah. Ainullah belongs to Commander Nazir Group, sources said.
The drone strike killed two Arab militants and two of their local allies and one was injured in Wana in South Waziristan Agency, they said.
Drone strikes in Pakistan resumed in June after a gap of six months when two successive drone strikes on June 11 reportedly killed around 16 people in Miranshah.
Pakistan launched a military operation in North Waziristan in June and the army says it has killed more than 1,000 militants so far.