The Gunners sit at the summit of the four-team section courtesy of their 4-0 beating of PSV Eindhoven and 2-1 win on Sevilla's turf either side of a narrow defeat at the hands of Ligue 1 side Lens.
Mikel Arteta's men are four points clear of Sevilla and PSV, meaning that victory on Wednesday would see them progress to the last 16 with two games to spare if Lens overcome the Eredivisie side.
However, Arsenal will welcome Sevilla to the Emirates drained both physically and mentally, having suffered back-to-back defeats to West Ham United and Newcastle United in the EFL Cup and Premier League respectively.
Arteta is also working without Jurrien Timber, Emile Smith Rowe, Thomas Partey and Gabriel Jesus due to injuries, in spite of the fact that the latter has been called up to the Brazil squad for November's international fixtures.
The Gunners are also sweating over the fitness of captain Martin Odegaard, who sat out Saturday's defeat at St James' Park following a hip issue, and Arteta is unsure whether he will be fit.
After addressing the media alongside Takehiro Tomiyasu, Arteta led a training session on the London Colney pitches, where Nketiah was notably absent from the rest of the group.
The England international is understood to be carrying a knock from the weekend's defeat to the Magpies, and he will require a late fitness test to determine his availability.
Nketiah is yet to start a Champions League game this season, coming off the bench against Lens and PSV in the last two matchdays, but he would have been expected to begin Wednesday's game amid Jesus's layoff.
However, with the 24-year-old now in the care of the medical team, Arteta is at risk of being without both of his recognised centre-forwards at the Emirates Stadium, which could see either Leandro Trossard or Gabriel Martinelli start through the middle.
Arteta is facing quandaries in all areas of the pitch, as Kai Havertz put in another mediocre display against Newcastle and controversially escaped a red card for a crunching tackle on Sean Longstaff.
Fabio Vieira and Mohamed Elneny will be the Spaniard's only alternatives if Odegaard misses out, though, while Oleksandr Zinchenko is a candidate to return to the backline.
Sevilla are also working around their own mini-injury crisis, though, as four-time Champions League winner Sergio Ramos has been ruled out of the clash with a calf problem.
Ramos is one of five defensive absentees for the Europa League holders, who are also without first-choice goalkeeper Orjan Nyland and one of his backups - Alfonso Pastor - owing to quadriceps and knee injuries.
Brazilian centre-back Marcao is sidelined with his own knee problem, while World Cup-winning left-back Marcos Acuna was another late withdrawal due to a hamstring issue.