The attack happened around 20:15 GMT in the Mangrotai area of Shawal district, South Waziristan, a tribal region considered a stronghold of Taliban insurgents.
"A US drone fired two missiles targeting a centre run by Uzbek rebels, killing four militants," a senior Pakistani security official told AFP.
Another security official confirmed the attack and casualties but said the identity of those killed in the strike was not immediately known.
A US drone strike on another Uzbek facility in the same area had killed at least five more militants, according to officials.
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These semi-autonomous areas have for years been a hideout for Islamist militants of all stripes -- including Al-Qaeda and the homegrown Tehreek-e-Taliban Pakistan (TTP) as well as foreign fighters such as Uzbeks and Uighurs.
Washington pressed Islamabad for years to wipe out the sanctuaries in the North Waziristan tribal area, which militants have used to launch attacks on NATO forces in Afghanistan.
The Pakistani military launched a major anti-militant offensive in North Waziristan in June and say they have killed more than 1,000 militants so far, with 86 soldiers losing their lives in the operation.
Pakistan routinely protests against US drone strikes, which have been targeting militants in the tribal areas since 2004, saying they violate its sovereignty and are counterproductive in the fight against terror.
But most analysts believe the resumption of the drone programme after it was suspended -- reportedly to give Pakistan space for negotiations with the Taliban -- is evidence of collusion between the two countries.
The Islamabad government and military officials strongly deny this.