Three drivers were among the five persons injured in the attack in Khairpur district of Sindh province, police said. The injured were taken to a nearby hospital. Doctors said two drivers were hit by bullets.
According to police, the incident took place late last night. The suspected militants fired at the oil tankers, which were going from the port city of Karachi to the northwestern city of Peshawar, and then torched them.
The flames from the tankers spread in minutes and burnt a roadside hotel and three shops. Traffic was suspended on the National Highway.
Fire tenders, facing problems because of the huge flames, managed to extinguish the fire after five hours, witnesses said.
Footage on TV showed the tankers burning on the highway. The suspected militants fled after the attack.
No group claimed responsibility for the incident. Police launched a search to apprehend the attackers but no one was arrested till this morning. Attacks by suspected militants on NATO trucks are common in Pakistan's restive northwest and southwest but such attacks are rare in Sindh province.
The tankers cross into Afghanistan via the Torkham land border crossing.
Hundreds of tankers and trucks pass through Pakistan every day, carrying oil and other supplies for some 150,000 foreign forces in Afghanistan.
Suspected militants routinely attack the NATO supply vehicles in Pakistan. This has forced the US to strike deals with Russia and some Central Asian states for alternate supply routes.
Pakistan is the shortest supply route to Afghanistan and officials say around 70 per cent of items required by the NATO forces are supplied through the country.