Pasquantino made his professional debut in 2019 with the Rookie-level Burlington Royals, batting .294 with 14 home runs and 53 runs batted in (RBIs) over 57 games.[3] He did not play in 2020 because the season was cancelled due to the COVID-19 pandemic.[4] He started the 2021 season with the Single-A Quad Cities River Bandits before being promoted to the Double-A Northwest Arkansas Naturals.[5] Over 116 games between the two teams, he slashed .300/.394/.563 with 24 home runs, 84 RBIs, and 37 doubles.[6]
Pasquantino opened the 2022 season with the Triple-A Omaha Storm Chasers. After the Royals traded first baseman Carlos Santana on June 27, Pasquantino was promoted to the active roster.[7] On July 1, Pasquantino hit a home run off of Detroit Tigers starter Michael Pineda for his first career major league hit.[8] He hit his second career homer on July 11, coincidentally also off of Pineda.[9] He was named the American League player of the week for August 8 to 14 when he hit .455 with four home runs and six RBIs in six games.[10]
Pasquantino made the Opening Day roster for Kansas City in 2023. Playing in 61 games, he hit .247/.324/.437 with 9 home runs and 26 RBI.[11][12] On June 14, 2023, it was announced that Pasquantino would undergo season–ending surgery to repair a torn labrum in his right shoulder.[13][14]
Pasquantino began the 2024 season as the Royals' starting first baseman. During a game versus the Houston Astros on August 29, Pasquantino suffered a broken right thumb when Astros catcher Yainer Diaz ran into his outstretched hand as he attempted to field a throw from pitcher Lucas Erceg. He underwent surgery which ended his regular season.[15] He played in 131 regular season games in 2024, slashing a combined .262/.315/.446 with 19 home runs, and 97 RBIs.[16]
Pasquantino and Ryann Harris announced their engagement in September 2022. Like Pasquantino, Harris attended Old Dominion University, where she played for the women's soccer team.[19]