Israeli Prime Minister Benjamin Netanyahu and President Biden spoke Wednesday as the Jewish state prepares for its retaliatory strike on Iran — with the Tehran theocracy warning of greater escalation if attacked.

The call, the first between the two men in 49 days, came as the US presses for a measured response by Israel to Iran’s ballistic missile barrage Oct. 1 that killed one Palestinian man in the West Bank.

Vice President Kamala Harris, the Democratic candidate for president, also joined Wednesday’s call.

The White House said that Biden “condemned unequivocally Iran’s ballistic missile attack against Israel,” but did not say what Biden and Harris counseled about anticipated retaliation.

Biden also discussed Israeli operations against Hezbollah in Lebanon and Hamas in the Gaza Strip, according to a readout.

The president “emphasiz[ed] the need to minimize harm to civilians [in Lebanon], in particular in the densely populated areas of Beirut,” it said.

“On Gaza, the leaders discussed the urgent need to renew diplomacy to release the hostages held by Hamas [and] the humanitarian situation in Gaza.”

The talk was expected to focus directly on the looming Israeli counterattack, with Biden opposing strikes on Iran’s nuclear facilities and oil reserves, sources told CNN.

White House press secretary Karine Jean-Pierre said the call lasted about 30 minutes and was “productive” and “direct.” 

Harris declined to discuss the call when asked about it by CNN’s Dana Bash during a Wednesday afternoon interview.

“It was a classified call,” the veep said, “and I don’t have any announcements to make about what happened during that call.”

Wednesday was also the first time Biden and Netanyahu have spoken since reports of their strained relationship featured in Bob Woodward’s upcoming book “War.”

The book, out next week,  claims Biden privately raged at and cursed out Netanyahu over his controversial invasion of Rafah earlier this year, and slammed the PM to his face for having “no strategy” in the war against Hamas.

The call also comes as Israeli Defense Minister Yoav Gallant accused Netanyahu of sabotaging his upcoming trip to the US to speak with his American counterpart in Washington about Israel’s response to Iran.

Netanyahu’s office denied the allegations and claimed Gallant’s trip was never approved, the latest clash between the two Israeli officials.

As Israel prepares for its direct attack on Iran, Tehran has warned that any strike from the Jewish state could result in a retaliatory attack against civilians.

Ebrahim Rezaei, a spokesperson for Iran’s National Security and Foreign Policy Commission, said Iran kept its Oct. 1 assault to military targets, but that alleged restraint would be lifted if the conflict escalates.

“There are other targets that we could hit, and we have the capability to do so,” he told CNN. “Our response will be forceful and hard.”

With the two nations promising to retaliate against any attack, fears continue to rise over the possibility of an all-out war in the Middle East between Israel and Iran and its terror proxies.

Rezaei ultimately called on the US to rein in Israel and push for a cease-fire in Gaza to end the ongoing conflicts in the region.