Palestinian medical sources told Aljazeera correspondent Samir Abu Shamalah, the air strikes early on Sunday hit a motorcycle travelling through the city's al-Zaitun district, "wounding at least nine civilians".
Hamas sources named one of the dead men as Wael Nassar, 38, a senior leader of one of Hamas's military wings.
Abu Shamalah said Nassar had been an Israeli target for ten years and had survived numerous attacks and assassination attempts.
Hamas resistance fighter Muhammad Sarsur, 31, also died in the attack.
Civilians in crossfire
A civilian, Madi Abu Madi, 18, was also killed.
Three of the wounded civilians were in critical condition. A woman and two children were among the casualties, hospital sources said.
Witnesses said two of the three dead were riding the motorcycle.
The Israeli army had no immediate comment on the incident.
Israeli occupation forces killed 16 Palestinians and wounded 185 in a two-day siege of al-Zaitun earlier this month. Palestinian resistance fighters hit back, blowing up a troop carrier carrying six Israeli soldiers.
All six were killed.
Palestinian fighters killed another five soldiers in the same way shortly afterwards in the southern town of Rafah, prompting a six-day army siege of the area that left 42 Palestinians dead and more than 1000 homeless.