Howe's side must beat Milan at St James' Park in their final Group F match and hope Paris Saint-Germain drop points against Borussia Dortmund if they are to make the last 16.
After waiting 20 years to return to the Champions League, Newcastle are desperate to extend their adventure in Europe's elite club competition.
But, hampered by injuries, Sunday's dismal loss at Tottenham in the Premier League suggested they could be running out of steam at the worst possible time.
"We'll look at the game and try and analyse it properly to work out who to select on Wednesday. We're not aflush with options," Howe said.
"It is difficult because we play on Wednesday. We hoped to have the squad to cope with that, but we've had worse injuries than any team that I can remember.
"These last few games have been tough, but I think the lads are giving everything."
After a 3-0 loss at Everton on Thursday, Newcastle were outplayed and outfought in north London as Destiny Udogie and Richarlison put Tottenham two up before half-time.
Richarlison netted again after the break and Son Heung-min added a late penalty, with Joelinton's stoppage-time strike no consolation for weary Newcastle.
With Newcastle languishing in seventh place in the Premier League, seven points adrift of the top four, a return to the Champions League next season cannot be taken for granted.
That makes this season's campaign in the tournament even more significant for the Saudi-backed club, whose owners didn't buy the Magpies to watch them scrap to qualify for Europe's second- and third-tier competitions.
If PSG win against Dortmund, Newcastle will be eliminated regardless of their result against Milan.
But Howe hopes the return to fitness of England striker Callum Wilson and energetic midfielder Sean Longstaff, who both came off the bench against Tottenham, will prove a much-needed boost.
"We have light at the end of the tunnel. Callum and Longstaff are two huge players for us," he said.
Regardless of Newcastle's fitness woes, which have contributed to four defeats in their last seven games, Howe wants his team to use the pain of their spluttering streak as fuel for a dynamic display against Milan.
"We have to be positive, take the pain and come fighting," he said.
"It's a difficult moment for us. We probably expected it to come a little bit earlier than it has. I think the lads have been really good to sustain the results that we were having.
"The last two have been tough games. Not us at our best. Physically we looked fatigued and there was not much we could do about it.
"But we just have to keep going. The more players we can get back, everyone is so important."
