In a lengthy email sent to workers less than two weeks ahead of Microsoft releasing its quarterly earnings report, Nadella mixed encouraging words with a vow to shake-up the company and its culture.
"Tired traditions will be questioned," Nadella said in the email, a copy of which was shared with AFP.
"Our priorities will be adjusted."
From how the company is organized to job responsibilities and hires, changes should be expected, according to Nadella.
He again stressed a vision of adapting Microsoft to a "mobile-first, cloud-first world" and said that "nothing was off the table" when it came to achieving that goal.
The Redmond, Washington-based company also foresees mergers and acquisitions.
"If you want to thrive at Microsoft and make a world impact, you and your team must add numerous more changes to this list that you will be enthusiastic about driving," Nadella said in the email.
Microsoft will remain true to Xbox video game consoles as well as Surface tablets and Windows-powered smartphones that have had less success in the market, according to the company chief.
"The combination of many devices and cloud services used for generating and consuming data creates a unique opportunity for us," Nadella said.
"We will reinvent productivity for people who are swimming in a growing sea of devices, apps, data and social networks."
Outlined aims included delivering more natural ways to interact with computers and marketing devices that show off capabilities of the company's software.
Senior team leaders at Microsoft have been asked to come up with ways to innovate processes and simplify operations.
"Culture change means we will do things differently," Nadella said in the company-wide message.
"Often people think that means everyone other than them. In reality, it means all of us taking a new approach and working together."
In February, Nadella replaced Steve Ballmer at the Microsoft helm. He quickly called for the company founded in 1975 to think more like a startup.
Nadella's appointment coincided with Microsoft founder Bill Gates stepping back in as a "technology advisor," giving up his title of chairman.