Al Jazeera's Kamal Hyder reporting from Islamabad, the Pakistani capital, said: "No one is clear under what mandate the Americans are carrying out such strikes because this is the month of Ramadan and there is going to be a considerable backlash not just in those areas, but from across Pakistan.
"People are angered by the way the Americans are conducting their affairs in this particular conflict . This is an infringement of sovereignty.
"Aircraft with no pilots onboard are constantly flying into Pakistani aerospace and attacking targets within Pakistan ... it creates a very complex situation for the Pakistani military itself.
"The signal the Pakistanis want to send across is that they want to be able to work within their territory without outside interference."
Tuesday's attack was the second in the North Waziristan tribal region in less than 24 hours.
A similar strike targeting a madrassa (Islamic school) and an adjoining house in Machikhel village killed at least five people on Monday.
Residents on Tuesday said they had seen the drone hovering in the sky and had been expecting the missile attack.
Washington alleges Al-Qaeda and Taliban rebels who fled Afghanistan after the 2001 US-led invasion are holed up in the semi-autonomous tribal belt.