Amateur Santini spent his first two years of high school at
John F. Kennedy Catholic High School in
Somers, New York before moving to
Ann Arbor, Michigan to participate in the
USA Hockey National Team Development Program. Santini was rated as a top prospect who had been projected as a first round selection of the
2013 NHL entry draft. He trained with the
USA Hockey National Team Development Program team from 2011 to 2013, and won a Silver Medal with Team USA at the
2013 IIHF World U18 Championships where he was named the tournament's best defenseman. In his first season at
Boston College, Santini earned his role as a top-4 defensemen with the Eagles, garnering a reputation as a hard-hitting, shut-down defenseman, while also producing 3 goals and 11 points on the season. He was named to
Hockey East's All-Rookie team. He also played at the
2014 World Juniors for the United States. Santini started his sophomore campaign paired with freshman
Noah Hanifin as the top-2 defenseman for the Eagles, however, he only played in four games to start the season before being shut down due to a wrist injury. He underwent surgery, missed 16 games and returned to the lineup after the New Year's break. He scored one goal and assisted on 19 as a junior, while helping the BC Eagles to a
Frozen Four appearance where they fell short to Quinnipiac.
Professional He signed a three-year entry-level deal with the New Jersey Devils of the National Hockey League on April 9, 2016. He played his first NHL game later that night against the
Toronto Maple Leafs. Santini scored his first NHL point in his
2016–17 NHL debut, during a 3-0 win over the
Boston Bruins on January 2, 2017. He scored his first NHL goal on January 12, 2017, against the
Edmonton Oilers, due to a puck deflecting off his elbow. The Devils ended up losing in overtime 3–2. As a
restricted free agent, Santini signed a three-year, $4.25 million contract with the Devils on August 14, 2018. On June 22, 2019, Santini was traded by the Devils along with prospect
Jérémy Davies and draft picks to the
Nashville Predators in exchange for
P. K. Subban. In the following
2019–20 season, Santini struggled to make an impression with the Predators, appearing in just 2 games over the course of the season while playing the majority of the campaign in the AHL with affiliate, the
Milwaukee Admirals. On October 7, 2020, Santini was placed on unconditional waivers by the Predators for the purpose to buyout the remaining year of his contract. On October 10, Santini signed as a free agent to a one-year, two-way contract with the
St. Louis Blues. Following three seasons within the Blues organization, Santini left as a free agent and was signed to a one-year, two-way contract with the
Los Angeles Kings on July 1, 2023. In the season, Santini played exclusively with the Kings AHL affiliate, the
Ontario Reign, placing second on the team in scoring from the blueline with 5 goals and 20 points through 64 regular season games. Leaving the Kings at the conclusion of his contract, Santini was signed to a one-year, two-way contract with the Tampa Bay Lightning on July 1, 2024. ==Personal life==