The raid came after US, Qatari and Egyptian mediators resumed talks aimed at securing a truce and hostage-prisoner swap in the nearly eight-month war triggered by Hamas's October 7 attack on Israel.
The military said it had "eliminated" several militants in a "precise strike on a Hamas compound embedded inside an UNRWA school" just before 2:00 am in the Nuseirat area of central Gaza.
UN chief Antonio Guterres condemned the strike as "just another horrific example of the price that civilians are paying".
"There will need to be accountability for everything that has happened in Gaza," his spokesman Stephane Dujarric said.
The United States called on Israel to be "fully" transparent about the strike.
"The government of Israel has said that they are going to release more information about this strike, including the names of those who died in it. We expect them to be fully transparent in making that information public," State Department spokesman Matthew Miller told reporters.
EU foreign policy chief Josep Borrell called for it to be "independently investigated".
Israel accuses Hamas and its allies in Gaza of using schools, hospitals and other civilian infrastructure including facilities run by UNRWA, the UN agency for Palestinian refugees, as operational centres -- charges the militants deny.
The Al-Aqsa Martyrs hospital in Deir al-Balah, near Nuseirat, said it had received the bodies of at least "37 martyrs" from the strike.
Faisal Thari, a displaced Gazan who had sought refuge at the school, told AFP: "Why? What have we done for them to bomb us?"
Hamas in a statement decried a "new crime... against our people".
A medic said another Israeli pre-dawn strike killed six people in a house in Nuseirat refugee camp, and witnesses reported intense shelling in the Bureij and Al-Maghazi camps in the same area.
Israeli warplanes also carried out strikes in parts of Rafah, a source in Gaza's southernmost city told AFP.