"We must give a strong response to the terrorist Zionist regime. We will show the Zionists no mercy," Khamenei posted on X.
Israel last week launched an unprecedented bombing campaign hitting Iranian nuclear and military facilities, as well as residential areas.
Iran has responded by launching missiles and drones, and early Wednesday said it had fired hypersonic missiles at Israel.
On Tuesday, Trump demanded the Islamic republic's "unconditional surrender" and boasted that the United States could easily assassinate Khamenei, reports BSS.