The controversial Italian rider was on the brink of the biggest win of his career after breaking away and stretching his lead to 90 seconds.
However, tragedy would strike twice for the 27-year-old with first a puncture 29km from the line and then a crash not long after a forced bike change.
Moscon's misfortune allowed the chasing pack the chance to catch and then drop the Ineos Grenadiers rider with 16km to go.
"The tyre pressure was different," Moscon said of his bike change.
"After five hours of racing maybe the pressure had gone down and, as soon as I went on this bike, I felt different on the pavé. Maybe it was because of that that I crashed, but the sector was really slippery.
"I tried to attack from far out and gave everything I had. I just had a little bad luck with the puncture and then I was a bit on my limit. When you are on the limit, you make mistakes.
"I crashed, but I didn't lose too much time. But then they came back from behind and I didn't have the legs to follow them. I tried. Fourth place – we will try again next year."
Moscon pulled away from a leading group in the cobbled sector of Auchy-lez-Orchies to Bersee 49km from the line as the sun pierced through the clouds and the roads started to dry.
Entering the key cobbled sector of Mons-en-Pevele, Moscon led Vermeersch and fellow Belgian Tom Van Asbroeck by 35 seconds and Van der Poel, Canada's Guillaume Boivin and Colbrelli by 1:10.
Powering his way through the thick mud, Moscon extended his advantage over the Van der Poel trio to 1:25 as Belgian Wout van Aert faded away.
With 38km remaining, Vermeersch and Van Asbroeck were reined in by Van der Poel and company and the newly formed group organised the chase behind Moscon.
The Italian lost some 30 seconds with a flat rear tyre that prompted a bike change 29km from the line with the chasing quintet reducing the gap to 45 seconds.
It fell to 15 seconds after he crashed on a muddy patch but the Italian stayed just clear as Boivin crashed in the group of chasers in the cobbled sector of Camphin en Pevele.
He was however caught and dropped 16km from the finish in the Carrefour de l'Arbre as Colbrelli, Van der Poel and Vermeersch went clear to contest the final sprint.
"Who knows," he said when he was asked if he could've won without his bad luck.
"You can't say that now. The race went like it did. I also don't know exactly how much time I lost because of the two incidents.
"This race is, I think, the most beautiful race in cycling. It was very spectacular race. I tried to put my cards on the table early by attacking early, but it didn't work out. Another Italian won, so we can be happy as a nation anyway."