Israeli sources reported on Thursday night that shooting along Dizengoff Street, one of Tel Aviv's busiest streets left at least two dead and 10 others critically injured.
Israeli police and the Tel Aviv municipality called on residents to remain in their homes and stay away from their windows as panic has gripped the city.
At least four of the wounded were said to be in critical or serious condition, according to Sourasky Medical Center.
The agent behind the shooting has not yet been identified, but it is highly likely that it was a resistance operation like two nights ago.
Two Israeli soldiers were killed, and 12 others were wounded during an operation in the northern Palestinian city of Al-Khadira last Sunday.
Palestinian resistance groups have repeatedly stated that such actions are a natural response to the crimes of the Zionist occupiers against the oppressed people of Palestine.
Mahmoud al-Zahar, a senior member of the Palestinian Islamic Resistance Movement (Hamas), in an exclusive interview with the Iranian Press News Agency, said: "Operation Al-Khadira was a slap in the face of those who compromised and collaborators of the occupying Israeli regime."