Extra asked the 45-year-old if he would consider getting back together with Handler, to which he simply answered, "No."
"She thinks Cuomo, Italian guys — Italian hunk — she thinks he’s cool," the "In Da Club" singer said.
However, 50 Cent seemed to have nothing but love for the comedian. "Chelsea’s a good friend of mine. Whatever she says is fine with me. I don’t care what she says," he said. "A part of her show is almost to be unpredictable, and unpredictability is what makes a comedian."
The pair dated for several months in 2009 when they met on her show, Chelsea Lately.
The blonde beauty previously slammed her ex for supporting President Donald Trump and said that if the rapper changed his tune and didn't vote for Trump, she would reconsider her feelings toward him.
"I might be willing to go for another spin, if you know what I'm talking about," she told Jimmy Fallon.
Handler claimed she "had to remind 50 Cent that he was a Black person, so he can’t vote for Donald Trump."
“That part where she says 'if he decided to not support Donald Trump, maybe I give him another round' might have been more influential than that part," 50 Cent quipped.
The "Intro" singer — who appeared to support Trump this year — also cleared the air as to who he backs for president.
"I turned down a million dollars to go the inauguration (in 2017) — why would I just switch gears now?” he said.
50 Cent was heavily criticized when he supported Trump after seeing Joe Biden’s alleged tax plans in October. “WHAT THE F**K! (VOTE For TRUMP) IM OUT,” he wrote on Twitter when he saw Biden’s proposal to raise taxes for those earning over $400,000.
"F**K NEW YORK The KNICKS never win anyway," he wrote. "I don’t care Trump doesn’t like black people 62% are you out of ya f**king mind."
He revealed later that day that he is actually bankrupt, but fans were unsympathetic. "50 Cent can go f**k himself for choosing his personal wealth over the health of the nation. What a selfish piece of s**t," one user wrote. "Pay your fair share. You're rich stop acting broke," another said.
This came after 50 Cent publicly spoke out against Trump in 2016. "Let us pray, lord please don’t let Trump into office. We will spin out of control," he said at the time.