Witnesses told Ma'an that Israeli forces fired two missiles at a military site operated by the Al-Quds Brigades near Tal al-Sultan, northeast of the border city of Rafah.
Gaza medical official Adham Abu Salmiya said five were killed and 15 injured, four of them critically. The victims were transferred to Abu Yousef al-Najjar Hospital in Rafah, he said.
One of the deceased is Ahmad al-Sheikh Khalil, a prominent leader in the al-Quds Brigades, medics and Islamic Jihad officials said.
The other four were identified as Muhammad Ashour, Abdul Karim Shabat, Basem Abol Ata and Muhammad al-Khudari, also members of the Islamist faction's armed wing.
The al-Quds Brigades confirmed in a statement that one of its military sites in Rafah was attacked and a number of fighters were killed and injured.
Brigades spokesman Abu Ahmad said the strike was the most brutal on the resistance since April. A spate of rockets and airstrikes on Gaza killed at least 18 people in April before factions agreed a ceasefire.
Israel "wants to provoke the Palestinian resistance, and our response will target the heart of Israel," Abu Ahmad warned.
Confirming the strike, an Israeli army statement said military aircraft "targeted a terrorist squad in the southern Gaza Strip that was preparing to launch long-range rockets."
"A hit was identified and the launching attempt was thwarted," it said. "The aforementioned squad is responsible for the firing of the Grad rocket towards southern Israel this past Wednesday."
The rocket landed near the Israeli city of Ashdod, causing no injuries or damage, the army said Wednesday. Warplanes launched four airstrikes in central and southern Gaza early Thursday, causing no injuries.
The army said they were targeting "three terror activity sites" in central Gaza and a weapons facility.
Locals told Ma'an Thursday's strikes hit three open areas and a site used by Hamas' armed wing the al-Qassam Brigades in Khan Younis in the south and Deir al-Balah in central Gaza.
Later that day, Israeli forces fired on the Rafah area and lightly injured a Palestinian man, a health official said. The injured man was treated at the European Hospital.
Israel's army denied involvement in that incident.