McGuigan, along with son Jake, will travel to the States in the next two weeks to open serious talks with the promotional company which looks after the champion, Golden Boy whose representatives didn't make it to the Odyssey on Saturday night.
Santa Cruz has a growing reputation Stateside as one of the most entertaining fighters around and pound for pound king Floyd Mayweather has described him as one of his favourite fighters to watch.
McGuigan, who also took in Ulster's heroic defeat at the hands of Saracens in the Heineken Cup at the weekend, said: "It's not a question of if Carl fights Santa Cruz next, it's a question of when and where because this was a final eliminator so Carl is now the mandatory challenger.
"So, we will go out to America and get down to some serious negotiations with Golden Boy who are very keen on Carl. They want to make the Santa Cruz fight and other big fights for him.
"We want to bring the fight to Belfast and we have looked at Ravenhill which is a great venue, we have looked at the Balmoral Showgrounds for an outdoor fight as well and we have also thought about the Phones4U Arena in Manchester which used to be called the MEN Arena.
"We know it's not going to be easy bringing Santa Cruz out of America and it's going to take a lot to make that happen and we have to see if American television company Showtime who show Santa Cruz's fights are willing to come as well. So there's going to be long and hard negotiations.
"But you know, the Belfast fans deserve the world title to be in Belfast because they are the best in the world. You heard the atmosphere again, it was amazing – you won't get any better atmosphere in the world, the noise was sensational."
McGuigan has no doubt that Frampton can rip the WBC World title from the grasp of Santa Cruz, with the crushing defeat of Hugo Cazares simply compounding that belief.
McGuigan added: "We've seen Carl drop light-middles and welterweights in the gym and hurt them so any super-bantamweight in the world that he hits clean, he'll knock them out.
"And if he hits Leo Santa Cruz cleanly, he'll knock him out as well, no doubt, because he is so naturally heavy-handed.
"If you analyse the fight, he knocked Cazares out on the front foot. We have always known that he can do it off the back foot, he's comfortable there and always has been, but we have been working on him to make him better coming forward and he knocked out Cazares coming forward with the left hook."
Coach Shane McGuigan admitted that even he was surprised by how quickly the Jackal broke down the threat of 36-year-old Cazares.
Shane said: "I didn't expect the stoppage so early and I didn't expect the left hook, I thought the straight right hand would get him because when he goes to the ropes he gets square on.
"He knocked Martinez out when he wasn't trying to knock him out and he was only looking to set him up with the left hook before landing with the right hand, so it just shows you the power that he has."
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