To begin the 2021 season, Romero was assigned back to Montgomery, now members of the Double-A South.[16] After pitching to a 1-0 record with a 1.88 ERA and 75 strikeouts over 48 innings, he was promoted to the Durham Bulls of the Triple-A East in July.[17] He earned Triple-A East Pitcher of the Month honors for September after going 5-0 with a 0.31 ERA over five starts.[18] Over 12 total starts with Durham, Romero went 7-2 with a 3.18 ERA and seventy strikeouts over 62+1⁄3 innings.[19]
On November 19, 2021, the Rays selected Romero's contract and added him to the 40-man roster.[20] He returned to Durham to begin the 2022 season.[21] After his first start, the Rays promoted Romero to the major leagues on April 12 and he made his MLB debut that night as the starting pitcher versus the Oakland Athletics at Tropicana Field.[22] Coincidentally, the starting pitcher for the Athletics was Adam Oller, who was also making his MLB debut in the game.[23] He pitched 1+2⁄3 innings, giving up three earned runs on five walks, two hits, one home run, and one strikeout.[24] On July 14, Romero recorded his first career win after pitching a scoreless sixth inning against the Boston Red Sox.[25] He was designated for assignment on August 23, 2022.
Washington Nationals
Romero was claimed off waivers by the Washington Nationals on August 25, 2022. He was immediately optioned to the Nationals' Triple-A affiliate, the Rochester Red Wings.[26] On November 15, Romero was designated for assignment. On November 18, he was non–tendered by the Nationals and became a free agent.[27]
Romero re-signed with the Nationals on a minor league contract on December 14, 2022. He made 36 appearances (10 starts) for Rochester, compiling a 5–7 record and 5.44 ERA with 82 strikeouts across 87+2⁄3 innings pitched. Romero elected free agency following the season on November 6, 2023.[28]
San Francisco Giants
On January 25, 2024, Romero signed a minor league contract with the San Francisco Giants.[29] In 19 games (8 starts) for the Triple-A Sacramento River Cats, he posted a 4-1 record and 3.14 ERA with 66 strikeouts across 71+2⁄3 innings pitched. Romero elected free agency following the season on November 4.[30]