Inter approach the 2013-14 campaign as a mid-table prospect for the first time in over a decade after tumbling into a ninth-placed finish under Mazzarri's predecessor Andrea Stramaccioni.
A summer reboot was required and, after the long-term Napoli coach had been lured to San Siro, he set to work recruiting young talents Mauro Icardi, Ishak Belfodil and Saphir Taider while jettisoning the disruptive Antonio Cassano and aging midfielder Dejan Stankovic.
So dramatic was Inter's fall from grace that critics have sniffed at talk of a swift return to the title-chasing pack, but Mazzarri has ignored the naysayers while drilling his distinctive brand of technical football into his new charges.
He told inter.it: "I've always been used to letting the football do the talking, dealing only in the facts, and when the season starts you will see that.
"There's a lot of talk before everything kicks off, a lot of flag-waving, but I just pay attention to the facts because things generally turn out differently to how people say they will.
"I hope everyone understands that we are starting from scratch. The team is in the process of being rejuvenated and that takes time, but I think people will understand that."
Icardi - a promising Argentinian forward who arrived from Sampdoria - is set to partner countryman Rodrigo Palacio in attack while Cristian Chivu, Walter Samuel and Diego Milito miss out through injury.
Also handed a remit to restore a fallen giant to former glories is Fabio Liverani, who takes control of his first league game as Genoa coach.
The Ligurians narrowly avoided relegation at the end of last season and president Enrico Preziosi responded by promoting former Lazio winger Liverani from his role with the youth team.
While the 37-year-old is daunted by his first assignment, he is eager to learn how well the Rossoblu players have responded to his instruction.
"It's the perfect acid test to see where we're at," he told Genoa's official website.
"The days go by and the understanding improves but there's a long road ahead of us.
"We're expecting a great game against an illustrious opponent at an amazing stadium.
"I never dreamed I'd make my debut in such a tough match. It's not an easy start, that's for sure."
Midfielder Matuzalem is injured while defender Davide Biondini serves a one-match ban.