The Super Eagles striker returned from an injury scare to score the opening goal for Les Dogues at the Stade Louis II but Monaco recovered quickly to hand the visitors a 5-1 thrashing.
Victor Osimhen started yet again for Lille despite spending two days at the hospital earlier in the week, and the Nigeria international repaid his coach's trust by handing his side the lead inside 13 minutes.
It was the second time in two games against Monaco that the 20-year-old would be grabbing the opener, having done same in the 3-0 defeat of the Principality Club on Tuesday.
But Leonardo Jardim's men, unlike in midweek, responded in style to head into the break with a 2-1 lead thanks to goals from Gelson Martins and Keita Balde.
A Ben Yedder brace and another late strike from Kamil Glik completed the humbling of Christophe Galtier's side.
Osimhen's star, however, continues to shine bright with the former Sporting Charleroi forward now on ten Ligue 1 goals.
Elsewhere in the Ligue 1, Moses Simon played the entire 90 minutes, but he could not rescue Nantes from suffering a rare home defeat in the hands of Angers.
Ludovic Blas got the home side in front after just 17 minutes, but Antonin Bobichon headed home the equalizer for Angers five minutes into the second half. Angers completed the comeback as Farid El Melali netted the winner three minutes from time.
