Gaza's Jabalia refugee camp was hit for a second time during Israel's bombardment of the northern part of the territory.
The Israeli military said it killed another commander in the airstrike.
There have been no immediate reports on casualties but footage showed smoke billowing over the camp and people sifting through piles of rubble and carrying away the injured.
"It is a massacre," one witness said.
Others told international media outlets that Wednesday's attack was in the Fallujah district of the large camp.
The Israeli military issued a statement saying its fighter jets had struck a Hamas command and control complex in Jabalia "based on precise intelligence", killing the head of the Islamist group's anti-tank missile unit, Muhammad A'sar.
"Hamas deliberately builds its terror infrastructure under, around and within civilian buildings, intentionally endangering Gazan civilians," the statement said.
This is the second time the camp has been hit in 24 hours, after Tuesday's strike killed 50 people and wounded at least 150, according to Gaza's Hamas-run health ministry.
Ayed al Bazm, a spokesman for Gaza's Hamas-run interior ministry, said six bombs hit the area, with apartment blocks in residential areas damaged in the explosions.
Images from the scene showed people searching for survivors inside wrecked buildings, and people climbing through several large craters.
IDF spokesperson Daniel Hagari said it was targeting Hamas commander Ibrahim Biari, who it says was one of the leaders of the massacres in Israel on 7 October.
The strike is said to have killed several other militants and collapsed the group's infrastructure "in the building and underground".
"The purpose of that infrastructure was to carry out terrorist activities against our forces," Mr Hagari added.
European Union foreign policy chief Josep Borrell said he was appalled by the high number of casualties in Jabalia and he urged all sides to respect the "laws of war and humanity..."
The Israeli military says Hamas enmeshes its fighters in crowded residential districts and uses them as cover for command posts and weapons sites.
Hamas leader Ismail Haniyeh said Israeli hostages held in Gaza were subject to the same "death and destruction" that Palestinians have faced.
Fifteen Israeli soldiers were killed in Gaza fighting on Tuesday, the military said after next-of-kin had been notified, its biggest one-day loss since the start of the offensive.
"We are in a tough war," Netanyahu said. "I promise to all citizens of Israel: We will get the job done. We will press ahead until victory."
It comes as the first UK nationals cross the Rafah border from Gaza into Egypt on Wednesday evening.
The crossing will be opened for "controlled and time-limited periods to allow specific groups of foreign nationals and the seriously wounded to leave", the British government said.
It comes after Britons who attempted to make the crossing were turned back, despite hundreds of other foreign passport holders being allowed to cross. The first group of civilian evacuees crossed the border on Wednesday morning.
They included at least 320 foreign passport holders and dozens of severely injured Gazans, three Egyptian sources and a Palestinian official said, the first beneficiaries of the deal brokered between Egypt, Israel and Hamas.