The air strike reportedly killed four suspected militants in the Pakistani town of Miranshah, located in the North Waziristan province, according to reports by the BBC.
The area, situated on the northern end of the Afghan-Pakistan border, is home to a number of so-called safe havens for terror groups operating inside Afghanistan and Pakistan.
The airstrike is the third launched by American forces since March, when members of the Pakistani parliament formally demanded the end to all U.S.-led drone attacks.
That demand was one of many conditions Islamabad put on a prospective deal with the United States to re-open critical supply routes to Afghanistan.
Washington and Pakistan were reportedly close to striking a deal to reopen the routes, which have been closed to American and coalition forces since last November, during NATO's annual summit in Chicago on Monday.
But a Pakistani demand to increase the price-per-truck cost to the United States to move through supplies through the country, as well as other issues, eventually brought negotiations to a halt.
Afghan president Hamid Karzai and Pakistani prime minister Syed Yousuf Raza Gilani will discuss the supply route issue, along with how to handle suspected terrorist sanctuaries inside Pakistan, during talks set for late May.
U.S. drone strikes have been key to stemming deadly cross-border raids by terror groups based in Pakistan against American and NATO forces in Afghanistan.
These attacks by the Taliban and Haqqani network, a Pakistan-based terror group affiliated with the Taliban, have causes some of the fiercest fighting between coalition forces and the Afghan insurgency.
A number of top congressional lawmakers claim terror outposts in Pakistan remain one of the main challenges to a successful handover of security operations from U.S. forces to the Afghan army.
In 2009, Pakistani forces launched a massive offensive in South Warziristan against al Qaeda and Taliban strongholds in the region. However, Islamabad continues to refuse to take military action in North Waziristan, despite pressure from the United States to do so.