"Occupation forces fired a ground-to-ground missile against the car that was carrying members of the Izz al-din al-Qassam Brigades," a Hamas spokesman said, referring to the movement's armed wing.
"This crime will not go unpunished," Sami Abu Zuhri said. "This massacre shows the dangerous Israeli escalation against the Palestinian people and the resistance."
One of the dead was named as Mohammed abu Arab, a local Hamas commander.
Earlier on Monday, two rockets and two mortar rounds had been fired into Israel from Gaza, causing no casualties or damage.
Hamas has admitted firing mortars but not rockets into Israel since it took full control of the Gaza Strip in June after clashes with Palestinian security forces loyal to Mahmoud Abbas, the president and leader of the rival Fatah faction.
Other groups have continued to launch rockets causing some damage but few injuries or deaths.
The air strike came as Gaza struggled with a fourth day of power cuts caused by the shut down of generators at the territory's only power plant.
The European Union has suspended the financing of fuel deliveries for the plant until it receives assurances that Hamas authorities are not benefitting from the aid.