Security officials said a strike killed four al-Qaida-linked fighters at an abandoned girls' school they had taken over in North Waziristan, Sunday, The Washington Post reported.
The Wall Street Journal said the attack was in Miranshah, the capital of North Waziristan, and killed at least three people.
In a statement, Pakistan's Foreign Affairs Ministry condemned the attack as a violation of the country's sovereignty.
"Such attacks are in total contravention of international law and established norms of interstate relations," it said.
Ministry spokesman Moazzam Ahmad Kahn declined to comment on newspaper reports that Islamabad would skip a NATO conference May 20-21 in Chicago, where countries plan to discuss the withdrawal of international troops from Afghanistan beginning in 2014.
"No decision has been made yet" about whether to attend the North Atlantic Treaty Organization, Khan said.
Pakistan did not to attend an international conference in Bonn, Germany, in December to protest the killing of 24 Pakistani soldiers in November by U.S. helicopters along the country's border with Afghanistan. Pakistan also closed NATO supply routes used to deliver supplies to coalition troops in Afghanistan.
Pakistan's lawmakers demanded an end to drone strikes as a condition of resetting relations with the United States and a prerequisite to reopening the NATO supply lines. The U.S., in turn, has withheld military aid payments to Pakistan.
Pakistani politicians said new drone strikes, the first inside Pakistan since March 30, would complicate further negotiations, The Washington Post reported.
"There will be repercussions whether in the government or in the public or in the Parliament," lawmaker Aftab Khan Sherpao said. "In no case would we allow the NATO supplies now."
After two days of talks in Islamabad last week, Pakistani leaders told U.S. negotiators NATO convoys would not be allowed to move across Pakistan unless the United States unconditionally apologizes for the November airstrike, the Post said. The Obama administration expressed regret for the deaths, which it said were accidental, but the Pentagon says both sides shared blame.
A team of 10 negotiators, including State Department and White House officials, is in Islamabad working on reopening the NATO supply lines, a U.S. official told the Post.
"We haven't found a solution yet, but everybody wants to find one," the official said.