Unlike in the Bundesliga, teams that finish level on points in the UEFA Champions League are separated by their head-to-head record rather than goal difference. That means TSG's chances of progressing to the knockout stages are no longer in their own hands, as Lyon have the superior head-to-head record against Hoffenheim on account of away goals scored (3-3 in Sinsheim, 2-2 in Lyon).
However, TSG can still qualify for the Europa League regardless of results elsewhere. Should Julian Nagelsmann's charges pick up their first-ever Champions League win against Shakhtar Donetsk, they will be guaranteed a third-place finish and the accompanying Europa League spot. But Hoffenheim's progression in the Champions League is dependent on results elsewhere. Should they beat Shakhtar this week and the group's other game between Manchester City and Lyon ends with a favourable outcome, TSG will go into Matchday 6 with their hopes of going through still alive.
If TSG get a point against the Ukrainians, there will still be a chance of reaching the UEFA Champions League knockout stages. However, in this case too, Hoffenheim would be dependent on results elsewhere. A defeat will completely rule out their chances of progressing to the next round. It would also mean TSG no longer have their Europa League qualification hopes in their own hands. In the event of a defeat or a higher draw than 2-2, they would lose the head-to-head battle with Shakhtar Donetsk, meaning they would need to finish with more points than the Ukrainians after six rounds of matches in order to finish above them in the table and seal a third-place finish.