The 23-year-old, who missed Sunday’s WSL win over West Ham with a hamstring injury, got a 17th-minute goal with a smart finish after great control.
She then set up captain Kim Little for the second goal 15 minutes later.
Miedema got a second and Lisa Evans was on target early in the second half.
The Dutch forward was substituted with just over half-an-hour to go, but not before she had pounced on a defensive error to calmly slot past the home goalkeeper for the third.
Evans’ left-footed volley from close range came from a Beth Mead cross from the byeline, which was flicked up by a defender’s head, as she completed the scoring before the hour mark.
The English champions could have had more – Little had a first-half goal ruled out for offside, as did Danielle van de Donk after the break, while substitute Jordan Nobbs missed a gaping goal with a late header.
The Italian hosts, who finished second in Serie A last season, rarely threatened.
Captain Tatiana Bonetti hit the side-netting with their best effort during a rare purple patch midway through the first half while Ilaria Mauro a header easily saved by Manuela Zinsberger in the last minute.