The strikes included one attack on Tuesday night on a school sheltering hundreds of displaced Palestinians, which killed 27 people, officials from the Al-Aqsa Hospital said, including nine women and three children.
It was the fifth time since the war began that the school in central Gaza has been struck.
An early-morning strike on another school-turned-shelter in Gaza City killed 16 people, according to officials at Al-Ahli Hospital, while strikes on targets in other areas killed at least 16 others.
A large column of smoke rose and fires pierced the dark skies above the school shelter in Bureij, a built-up urban refugee camp.
The Israeli military had no immediate comment on the strikes.
Israel blames Hamas for the death toll because it operates from civilian infrastructure, including schools.
The new bloodshed comes days after Israel approved a plan to intensify its operations in the Palestinian enclave, which would include seizing Gaza, holding on to captured territories, forcibly displacing Palestinians to southern Gaza and taking control of aid distribution along with private security companies.
Israel says the plan will be gradual and will not be implemented until after US President Donald Trump wraps up his visit to the region later in May.
The war began when Hamas-led militants attacked southern Israel, killing 1200 people and taking about 250 hostages.
Israel's offensive has killed more than 52,000 people in Gaza, many of them women and children, according to Palestinian health officials, who do not distinguish between combatants and civilians in their count.
Trump on Tuesday stunned many in Israel when he declared that only 21 of the 59 hostages remaining in Gaza are still alive.
Israel insists that figure stands at 24, although an Israeli official said there was "serious concern" for the lives of three captives.
The Hostages and Missing Families Forum, a group representing the families of the captives, demanded from Israel's government that if there was "new information being kept from us, give it to us immediately".
It also called for Israeli Prime Minister Benjamin Netanyahu to halt the war in Gaza until all hostages are returned.
"This is the most urgent and important national mission," it said on a post on X.
Since Israel ended a ceasefire with the Hamas militant group in mid-March, it has unleashed fierce strikes on Gaza that have killed hundreds and has captured swaths of territory.
Before the truce ended, Israel halted all humanitarian aid into the territory, including food, fuel and water, setting off what is believed to the be the worst humanitarian crisis in 19 months of war.
Key interlocutors Qatar and Egypt said Wednesday that mediation efforts were "ongoing and consistent".
But Israel and Hamas remain far apart on how they see the war ending. Israel says it won't end the war until Hamas' governing and military capabilities are dismantled, something it has failed to do in 19 months of war.
Hamas says it is prepared to release all of the hostages for an end to the war and a long term truce with Israel.
