Dimitrov saved a match point to secure a 150th match win at the ATP Masters 1000 level in a gruelling match that finally came to an end after two hours and 48 minutes as the Bulgarian sealed a 6-7[6], 6-4, 7-6[3] win.
He fell 3-0 behind in the decider and appeared to be close to defeat, but found a way to battle back and then found the energy to get back in contention.
Even though the 33-year-old looked to have run out of energy long before the end of the match, but found a way to come through and could barely control himself as he tried to comprehend his victory.
After sharing a warm exchange with Cerundolo, Dimitrov could be heard asking tournament officials to delay his on-court interview as he asked for some medical assistance.
He appeared to be suffering from cramps, was drawing big breaths and after a lengthy period of treatment that included medics checking his blood pressure readings, Dimitrov made his way off the court with the help of medical officials.
"He was running on fumes at the end of the second set," said tennis legend Martina Navratilova as she summed up the worrying images of Dimitrov at the end of the match on Sky Sports Tennis.
"What an amazing effort from Grigor. He was down and just kept coming back. Cerundollo looked much less tired and I would have backed him to win, but Grigor did it.
"I've never seen a player collapse after the match they have won. The fact that he was still able to win when he was feeling this lousing was an amazing emotional and physical effort.
"At least he has got a day off to hopefully recover. He probably won't be playing tomorrow and will just do some light bike work to get the blood flowing.
"It was amazing that he was able to play this well when he felt so lousy about his prospects.
"It is a good thing that we have tie-breaks in the final set because one or both of them would have been taken out of here on a stretcher."
The challenge for Dimitrov will be to try and recover for his semi-final on Friday and there must be some doubts over whether he will be ready to compete after such a demanding battle.
Even if he fails to win his next match, his long run in Miami will give Dimitrov a huge lift after a challenging start to 2025 and it means he will be back in the top 20 of the ATP Rankings when they are updated on Monday.