The youth-focused show was originally set to take place inside Brooklyn’s Barclays Centre, before those plans were scrapped due to the health crisis.
Instead, the VMAs will host outdoor performances from across New York City’s five boroughs, with limited or no audience.
And the show will pay tribute to the frontline workers who risked their lives during the pandemic, MTV said.
Gaga and Grande each have nine nominations, including a video of the year nod for their dance-infused collaboration Rain On Me, which is recognised in seven categories.
The pop titans will team up for the world premiere televised performance of the song.
Other performers include Miley Cyrus, who is set to debut her new single Midnight Sky, K-pop superstars BTS and rapper Doja Cat.
Elsewhere, Canadian singer The Weeknd and pop sensation Billie Eilish both secured six nominations, with Taylor Swift on five and Drake, Dua Lipa, J Balvin and Justin Bieber all on four.
Actress Keke Palmer, a self-proclaimed “millennial diva”, will be on hosting duties as the Moon Person trophies are handed out.
And in response to the pandemic, MTV has introduced two new categories to reflect music created in lockdown: best music video from home and best quarantine performance.
The ceremony usually plays host to some of the most shocking pop culture moments of the year, with past highlights including Kanye West’s infamous on-stage tangle with Taylor Swift in 2009.
However, it is unclear what tone this year’s show will take, against a backdrop of a global pandemic, social unrest caused by racial tensions and a flailing economy.
The 2020 MTV VMAs take place in New York at 1am UK time on Monday.