With just one defeat to their name in the last 10 European fixtures on home soil, the Eastern European team are available at 23/10 (3.30) with dabblebet to come out on top here.
However, the Partenopei ran out 2-1 winners over Dynamo Kiev in their only previous Champions League visit to Ukraine on the first game of last season's competition, and are 23/20 (2.15) to collect all three points once again in this one.
Just two of the guests' last 13 away games in this competition have resulted in draws, but you can get odds of 23/20 (2.15) on them settling for a point on this occasion.
Having failed to qualify for the first time in eight seasons last time out, Shakhtar will be relishing their return to the big stage this campaign.
Neutral viewers should also be celebrating their renewed involvement if the last appearance is anything to go by, when their six group stage matches produced 21 goals.
Given this recent history, the game in Kharkiv could be one of the ties of the round when they take on Maurizio Sarri's always entertaining outfit.
Having failed to score just once but kept only one clean sheet in their previous 11 away matches in the Champions League main stage, last season's Serie A top scorers look set to ensure the hosts' trend of high-scoring matches continues.
All in all, odds of 4/5 (1.80) are not to be missed on over 2.5 goals being scored for Napoli's 10th Champions League game in 13, as well as a sixth in eight for Shakhtar.