The Israel Defense Forces (IDF) has ordered residents of Khan Younis to evacuate as it prepares to launch an "unprecedented attack".
People were ordered to move towards al-Mawasi in the west of the strip, in one of the largest evacuation orders issued by the Israeli military in recent months.
An Arabic statement shared by IDF spokesperson Avichay Adraee said the area "will be considered a dangerous combat zone", adding: "Terrorist organizations have brought you disaster. For your safety, evacuate immediately."
The IDF launched a major new Gaza offensive on Saturday named Operation Gideon's Chariots. Hospitals have said more than 100 people have been killed in the last 24 hours.
One woman from Khan Younis told BBC News that the new evacuation order - which also covers the areas of Bani Suhaila and Abasan - was her "worst nightmare".
Another woman, who is already living under an evacuation order in central Gaza, said she would not move "because there is no place to go".
The IDF said its aim was to "destroy the capabilities of terrorist organizations in this area".
Earlier on Monday, Israeli Prime Minister Benjamin Netanyahu said that Israel would "take control" of the whole of Gaza.
In a video posted on social media, he said: "We are engaged in massive fighting - intense and substantial - and there is progress.
"We are going to take control of all areas of the Strip, that's what we're going to do."
The IDF said it had struck 160 targets across the strip in the last 24 hours.
A warehouse containing medical supplies at the Nasser Hospital was hit by an Israeli strike overnight, Gaza's Hamas-run ministry of health reported.
British charity Medical Aid for Palestinians said the strike happened "as Palestinians who were killed and wounded from other attacks were being brought to the hospital".
"We are just seeing all our work being burned to ashes," a spokesman for the charity said.
Separately, Palestinian media reported that Israeli special forces troops dressed in women's clothing had entered a Khan Younis home undercover and killed one man on Monday morning, before arresting his wife and child.
Israeli media named him as Ahmad Sarhan, and reported he was a senior member of the military wing of the Popular Resistance Committees - a Palestinian militant group aligned with Hamas.
The IDF has previously said the expanded Gaza operations are aimed at "achieving all the war's objectives", including releasing hostages and "the defeat of Hamas".
But a group representing many of the hostage's families said the operation posed "grave and escalating dangers" to hostages still held in Gaza.
"Testimonies from released hostages describe significantly worsened treatment following military strikes, including physical abuse, restraint and reduced food," the Hostages and Missing Families Forum said.
On Sunday, Israel announced it would allow a "basic amount of food" to enter Gaza to ensure that "no starvation crisis develops" after blockading the territory for 10 weeks.
The war was triggered by the Hamas-led attacks on southern Israel on 7 October 2023, which saw about 1,200 people killed and 251 taken hostage.
Some 58 hostages remain in Gaza, up to 23 of whom are believed to be alive.
More than 53,000 Palestinians have been killed during Israel's military campaign in Gaza.
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