Defending champion Pogacar was toppled last week in a gruelling Alpine stage after coming under sustained fire from Vingegaard and his Jumbo Visma teammates, namely Primoz Roglic (32), but the Slovenian has vowed to fight until the end.
Despite a two minute and 22 second-deficit, the 23-year-old can still hope to win a third consecutive Tour.
On Sunday, Vingegaard hit the deck and sustained bruises on his left side while Steven Kruijswijk (35) crashed out and Roglic abandoned after failing to recover from a back injury.
It leaves Jumbo Visma down to six riders and with one of them, Tiesj Benoot (28), battered and bruised after also crashing on Sunday, the Dutch outfit could struggle to control the aggressive Pogacar.
"I need to grab every chance, use every climb there is. I need to try and attack," Pogacar told reporters on Monday.
"I will give everything and I hope I don't have any regrets."
Pogacar tried last Thursday on the climb to l'Alpe d'Huez but after being greatly helped by his team's fast tempo in the first part of the ascent, Vingegaard followed easily.
With Kruijswijk and Roglic out, the 25-year-old will be less protected.
"It's going to be a crazy third week," Groupama-FDJ sports director Philippe Mauduit, whose leader David Gaudu (25) is gunning for a top five finish in Paris, told Reuters.
Tuesday's 16th stage features two brutal category-one climb before the 17th and 18th stages take the peloton into some of the toughest climbs of the Pyrenees.
Vingegaard said he felt good despite his crash on Sunday.
"I slept well. I'm a bit bruised but I'm good. It stings a little but I'm not hurting," he said on Monday.
"I still have a two-minute and 22-second lead so we're good, even if losing two teammates is not a good thing."
Behind the leading duo is 2018 champion Geraint Thomas (36), who cannot match Vingegaard and Pogacar's explosivity but the Briton has so far managed to limit the damage and his Ineos-Grenadiers team have three riders in the top 10.
"I think up to this point Jonas has been the strongest, he's been able to respond to every attack as well and he's been riding cleverly," said Thomas.
"But it's a three-week race not 15 days."
Will Ineos-Grenadiers collide with Pogacar to unsettle Vingegaard?
"It's not like Pogacar is gonna be ringing me up and we're gonna make a plan tonight but once you're on the road if a situation comes where it works for both of us it's just like any other race," Thomas explained.
"But it's not like a vendetta against Jonas or Jumbo, but it's bike racing, so anything can happen."
The race takes on a 178.5km transistion stage into Foix on Tuesday. With two testing climbs towards the end of the stage, we will get a sense of how the race will pan out across the third week.
