Frampton won the WBA featherweight title against Santa Cruz in July last year but lost his unbeaten record in the rematch.
And in the wake of his first career defeat, the Northern Irishman revealed he wanted to settle the score with his Mexican rival back at home.
"We will have to do it again," Frampton said.
Carl Frampton admitted he was outboxed by Leo Santa Cruz in Las Vegas
"We have to do it again.
“He was very clever and he used his reach. I think he deserved it. I’m being honest.
"I think he deserved it. But it was a very good fight.
Carl Frampton was subjected to the first loss of his professional career
"I think I can perform slightly better. No excuses.
“Let’s do it again. I hope he’s a man of his word and comes to Belfast. I hope he does.”
The fight drew a massive crowd at Vegas' famous MGM Grand with more than 4,000 people making the trip across from Northern Ireland.
Leo Santa Cruz has also only lost once in his career
But they could not roar Frampton to victory as he was unable to match the skill of his 28-year-old opponent.
“It was a very tough fight," Frampton added.
"Some of the rounds were close.
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"I really think Leo deserved it.
“He told me what he was going to do. The brawler was out-boxing the boxer.
"My fault. I’m sorry."