Hummels had to be withdrawn at half-time in Dortmund's 2-0 win over Wolfsburg because of an Achilles problem on Saturday, as Emre Can made his return from the bench.
Dortmund's sporting director Michael Zorc later revealed the FIFA World Cup winner was suffering with a long-standing issue.
Dortmund faces defending Bundesliga champion and leader Bayern Munich at Signal Iduna Park in Der Klassiker on Wednesday (AEST).
Zorc said of Hummels, who spent three seasons at Bayern before returning to Dortmund: "I spoke briefly to the doctor. Mats has a complaint with his Achilles tendon.
"He has had this from training for a long time. But we hope that he can play again on Tuesday [Wednesday]."
Head coach Favre added: "I can't tell if he will play or not. I hope that he will be back."
Sancho's involvement in the crunch top-of-the-table clash is also in some doubt despite an impressive cameo at Wolfsburg.
The England winger earned his 16th assist of the season as he teed up Achraf Hakimi for the second goal, adding to the in-form Raphael Guerreiro's first-half opener.
⚽️ GOAL!! @AchrafHakimi finishes, but this is all @Sanchooo10. His 16th assist of the season 🔥— beIN SPORTS (@beINSPORTS_AUS) May 23, 2020
@VfL_Wolfsburg 0️⃣-2️⃣ @BVB
Watch LIVE on CONNECT @kayosports, @Foxtel & Fetch!! ▶️ https://t.co/UXdkBwTm4p#Bundesliga | #WOBBVB pic.twitter.com/eHUwvlmU7Y
But Sancho was again only appearing from the bench, as he had against Schalke, after a calf injury upon his return from the coronavirus-enforced break.
Any assumptions Sancho was simply being rested in order to start against Bayern were seemingly dismissed by Favre.
"He's only been training with the team for 10 days. That is not much," Favre said. "I can't say for sure if he will play."