Tiara Brown and Oshae Jones will put their world championships on the line against Hannah Rapp and Elia Carranza on June 13 at Caribe Royale Resort in Orlando, Florida.
WBC featherweight titlist Brown, who has beaten Skye Nicolson and could be a future opponent for Britain's Ellie Scotney, will box Hannah Rapp.
"I'm going to show the world why I should never be overlooked and taken lightly," Brown said.
Jones, the IBF super-welterweight belt-holder and an Olympic bronze medallist, will rematch Elia Carranza after the champion's split decision victory over her last year.
Also on the Most Valuable Promotions (MVP) bill, Tampa's WBA super-flyweight world champion Jasmine "Animal" Artiga will make a third world title defence against a to-be-named opponent.
Rounding out the main card, unified WBO, WBA, and IBF light-flyweight champion Evelin Bermudez of Argentina makes her promotional debut against Mexico's IBF No 1 contender Estefany Alegria.
Oshae Jones said: "This isn't just another fight for me; it's a moment to help elevate the sport, inspire the next generation, and create opportunities that will change countless lives. I'm proud to be part of something that is pushing women's boxing to new heights and making history."
Joining the card, MVP's undefeated Brazilian boxer and influencer Jully Poca, the most-followed active female boxer in the world, will make her professional debut. Also on the undercard will be MVP's two-time Brazilian Olympian Keno Marley and Boxlab Promotions' undefeated Gabriela Tellez and Jordan Orozco Hernandez.
"MVPW-04 is another powerful statement from MVP as the definitive global powerhouse in women's boxing, as we continue to showcase the deepest, most elite roster in the sport," said Jake Paul and Nakisa Bidarian, co-founders of Most Valuable Promotions.
"This card embodies exactly what MVPW was built for: high-stakes, world championship matchups featuring the best fighting the best.
"This event also proudly shines an international spotlight on Brazil's boxing scene, featuring the highly anticipated professional debut of Jully Poca and the return of two-time Olympian Keno Marley.
"We look forward to bringing another unforgettable night of MVP boxing back to Orlando."
