Prime Minister Benjamin Netanyahu has warned Israel's enemies they "put themselves in existential danger" if they attack the Jewish state.
At a ceremony inaugurating a joint US-Israeli missile interceptor, Mr Netanyahu said defending the home front is of the "utmost importance."
He went on to warn "whoever tries to strike us will be hit, those that threaten our existence put themselves in existential danger."
David's Sling, meant to counter medium-range missiles possessed by Iranian-backed Hezbollah militants in Lebanon, officially became operational at the ceremony, the military said.
It marks the completion of the multi-tier system that includes the Arrow, designed to intercept long-range ballistic missiles in the stratosphere with an eye on Iran, and Iron Dome, which defends against short-range rockets from Gaza.
Arrow was recently used to intercept an anti-aircraft rocket fired at Israeli fighter jets by Syria last month.
The Israeli military said it shot down one of several anti-aircraft rockets fired at its warplanes by Syria last week in the most serious military exchange between the two hostile neighbours in recent years.
Air force officials said four Israeli jets on a mission to destroy a weapons convoy destined for the Iranian-backed Lebanese militant group Hezbollah were attacked by three Syrian surface-to-air missiles, one of which was intercepted by Arrow.
Israel's defence minister threatened to destroy Syria's air defence systems "without the slightest hesitation" if they were used to target Israeli war planes again.