The Tigers will meet the Storm, with the Eels to face the Titans on Sunday February 28 (AEDT) at Allegiant Stadium for the penultimate year of the league's Vegas contract.
Heading into round 12 of this NRL season, none of the four participating teams are in the top eight, with only the Tigers sitting higher than 13th.
The quartet's selection leaves the Dolphins as the only team participating in this year's premiership that have not yet taken part in the Vegas showpiece event.
Expansion sides Perth and the PNG Chiefs would also have entered the competition in time for the final year of the NRL's deal in 2028.
Melbourne and Parramatta both had membership bases of more than 30,000 fans last season so are poised to welcome a large contingent of supporters to the US.
The Tigers' inclusion comes despite previous chief executive Shane Richardson famously claiming the club had no interest in playing in Vegas.
Their Vegas season opener will mark the start of Jarome Luai's final season at the Tigers, with the four-time premiership winner joining the Chiefs thereafter.
It remains to be seen whether master coach Craig Bellamy, contracted through 2028, will be in charge of the Storm for the Vegas match and beyond given his recent health diagnosis.
The Eels' Vegas game will come amid celebrations for the club's 80th anniversary.
"There's no better time for the Parramatta Eels to head to Las Vegas, and we're ready to showcase our club to the world," said chief executive Jim Sarantinos.
"With more than 37,000 members and thousands of passionate fans already expressing interest, we're expecting a huge blue and gold contingent in Vegas."
The likes of Jaydn Su'A (Eels), Jamayne Isaako (Storm) and Mawene Hiroti (Titans) are all in line to play their first matches for their new clubs in the United States.
English Super League sides Bradford and Leigh will also clash in Vegas, the latter coached by ex-Sydney Roosters and Maroons halfback Adrian Lam.
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