Isaac first attended Barron Collier High School in Naples, Florida during his freshman and sophomore years.

However, as a result of wanting to be reclassified as part of the high school class of 2016, Isaac also attended IMG Academy for what was considered to be a postgraduate year in 2016.

[2][3] On July 5, 2015, Isaac confirmed that he was going to commit to Florida State after his senior year of high school ended.

[5] Four days after making that announcement, however, Isaac confirmed that he was not going to enter the 2016 draft after all and reaffirmed his intentions of playing with Florida State for the 2016–17 season.

[7] On January 18, 2017, Isaac recorded 23 points, 10 rebounds, and a season-high 7 blocks in a win over the Notre Dame Fighting Irish.

As the second seed in the ACC tournament, Florida State beat Virginia Tech in the quarterfinals, but lost to Notre Dame in the semi-finals.

[9] In addition to that, Isaac announced his intention to forgo his final three years of collegiate eligibility and enter the 2017 NBA draft where he was projected as a lottery first round selection.

[15] On January 1, 2020, he suffered a posterior lateral corner injury and a medial bone contusion in his left knee during a 122–101 win over the Washington Wizards and was expected to be sidelined for about eight to ten weeks.

[16][17] On August 2, Isaac suffered a torn left anterior cruciate ligament (ACL) during a 132–116 win over the Sacramento Kings hosted in the 2020 NBA Bubble.

[18][19] Isaac later underwent successful surgery on August 7 to repair his torn left ACL and meniscus, and was expected to miss the remainder of 2019–20 NBA season.

[20] On August 31, Magic team president Jeff Weltman confirmed Isaac would also miss the entire 2020–21 season with the injury.

[24] On January 23, he returned to the court after over two and a half years, recording 10 points, 3 rebounds, and 2 steals in 9 minutes in a 113–98 win over the Boston Celtics.

[25] On February 28, during practice in Milwaukee, Isaac felt discomfort, and an MRI a day later revealed a torn left adductor muscle.