Matthews has missed Toronto’s past 10 games with a shoulder injury. The Leafs went 5-3-2 in his absence.
The 20-year-old has 28 goals and 22 assists in 53 games this season.
Maple Leafs defenceman Nikita Zaitsev will also be available versus Nashville. The defenceman has not played in a game since March 5 due to an illness.