Vargas (29-3-2 11 KOs) returns to the ring for the first time since his narrow reversal at the hands of Mikey Garcia in Texas in February 2020.
The former two-weight world champion is hungry to become a three-time ruler, and the 32-year-old is training for the Smith clash while running his political campaign to represent Nevada's 4th Congressional District.
Smith (30-3-1 17 KOs) will defend the WBA International strap he won in his last outing, where he stopped local rival Anthony Fowler in eight rounds in October at the M&S Arena in Liverpool, bouncing back in style from a slender loss in Russia to Magomed Kurbanov in May.
The 33 year old held the WBO World title in 2015-16, and now sits at #4 in the WBA rankings and eyeing two-time World champion status.
Vargas and Smith were due to meet this weekend in Phoenix, but Covid-19 ruled the former out of the clash and Saturday's bill will now be topped by Carlos Cuadras and Jesse Rodriguez battling for the vacant WBC World super flyweight title live worldwide on DAZN. Vargas and Smith will come to the Big Apple all guns blazing, and both men believe they will end the career of the other on April 30.
"Thankfully I'm now through Covid-19," said Vargas. "I want to show everyone I'm better than before, I've been working on things in the gym, so it's not like I've had a two-year lay-off.
"Liam is talking a lot, the fire is burning inside me. You don't trash talk me, I'm coming in a different person. This will be an action-packed fight. I'll exploit all of his weaknesses and take him out - My goal is to knock him out and retire him!
"It's going to be an amazing night. Amanda and Katie are trailblazers for the sport, and I'm honoured to be a part of an historic event in New York."
"I'm buzzing and proud to be fighting at Madison Square Garden," said Smith.
"It's one I can tick off my bucket list now along with Las Vegas; MSG is the pinnacle of boxing and everything happens for a reason so I am happy to be heading to New York on April 30.
"The main event is fantastic, Katie is always in exciting fights, and I am sure there will be lots of British and Irish fans there that will be backing me too.
"This fight is an itch that has needed scratching for a long time now and I want to beat Jessie and beat him well and move on. I hope that he turns up fit and healthy this time as I am aiming to retire him and send him into politics. He wants to move into politics, and I will give him a reason to concentrate on that 100 per cent.
"Jessie stopping me? I find that highly unlikely when only one person has done that and Jessie is no Canelo Alvarez. I fully intend on stopping him, being the first man to do it and adding my name to the names that have beaten him."