The unmanned spy plane targeted the compound belonging to a tribal elder in Sheen Warsak area of South Waziristan, one of the seven semi-autonomous districts in the tribal belt bordering Afghanistan.
Militants were present in the house, officials were quoted as saying by TV news channels.
Four militants were killed and two others injured in the drone attack, they said. The identity of those killed in the missile strike could not immediately be ascertained. There have been more than 40 drone strikes in the tribal region this year.