The pilotless plane hit the militants' compound in Birmal area of South Waziristan.
A security official said four rebels including a foreign militant of Arab-origin were killed in the attack and the compound was completely destroyed.
There are also reports that some militants were also injured.
The killed Arab was identified as Adil while the exact identity of others was not known.
South Waziristan, adjacent to North Waziristan, was cleared of militants in 2009 but still they are active in its remote areas.
South Waziristan is one of the seven lawless tribal districts of Pakistan that border Afghanistan.