Oscar-winner Bardem and Cruz signed an open letter speaking against "the genocide perpetrated by the Israeli occupation army".
The letter accused Israel of "advancing on Palestinian territories instead of withdrawing to the 1967 borders.
"Gaza is living through horror… while the international community does nothing."
The Spanish letter was signed by 100 leading figures in the film industry, including director Pedro Almodovar.
One top producer who has worked with Cruz says he privately has vowed not to hire her again, according to the Hollywood Reporter.
Another top Hollywood executive also privately expressed his disapproval, saying he's "furious at Javier and Penelope" and wasn't sure about working with the Spanish couple again.
Relativity Media chief executive Ryan Kavanaugh was the only studio head willing to go public with his views: "As the grandson of Holocaust survivors, I know that anyone calling what's going on in Israel 'genocide' vs. self-defense is either ignorant and shouldn't be commenting or is truly anti-Semitic."
However, Kavanaugh doesn't believe the letter will harm either of the actors' careers as long as their films are box office hits.
As one film producer explained: "I think the thing any executive or producer will try to calculate before working with Penelope Cruz or Javier Bardem in the near future is what their value is in the all-important international marketplace. And what territories they might have alienated people in by what they said. It might not be that many. But it's really all about business."
Other Hollywood big names have waded into the controversy, including comedian Joan Rivers. When quizzed by a TMZ reporter on her thoughts about the 2,000 Palestinians who have so far been killed, she said: "Oh my God! Tell that to the people in Hiroshima.
"Good. Good. When you declare war, you declare war. They started it. We now don't count who's dead. You're dead, you deserve to be dead. Don't you dare make me feel bad about that.
"They were told to get out. They didn't get out. You don't get out, you are an idiot. At least the ones that were killed were the ones with low IQs."
Watch Joan Rivers give her views on the Gaza Conflict