Looking back last year, over the course of 17 games regular season, I noticed two things.
1. The defense has deficiency in stopping the runs. Titans, Indy, and 1st Pats games are proof that teams can pound the rock on the Bills to score and limit possessions to Allen to win.
2. If D-line can get into Allen's face consistently, they will force bad games from Allen to win. Steelers and Jaguars games are proof of that.
This off-season, most people will point to Von Miller signing as the biggest impact to address defense. To me, that's for the playoff, for one game that you must have, you need that superstar doing superstar things that good players cannot do. Honestly I don't expect Von to do that consistently in regular season. He's past his prime at his age. The signings of DaQuan Jones and Tim Settle are more directly at addressing 1 above. We really don't have the linebackers who excel at stopping the run.
This Rams game is about dealing with 2. Across the line they have a good D-line staring Aaron Donald, who by himself, can wreck the Bills game plan, more so than Josh Allen of the Jaguars did to the Bills last year. If the Bills can somewhat keep him quiet, I would be very confident the Bills walk out Thursday night celebrating win #1.
If you watch the the Patriots/Rams superbowl, Belichick triple teamed on Donald a lot because Brady was a stature back there. The downside is that it limited options to Pats offense and Brady has very few people he can target.
Back in 2020, the Bills took a different approach under Daboll. They used a second layer blocking, leveraging Mitch Morse mobility as the last guy to fend off Donald when he broke through double teams. See the video below when they discussed Morse having an eye on Donald a lot (around 6:19 mark)
One variable I see this game is the running attack from the Bills. They added Safford which is a much better run blocker than a pass pro at this point. And they brought back Kromer which is one of the best known blocking scheming O-Line coaches - you can see in pre-season how many wide gaps the O-Line is creating for the backs. But I still believe the game will be won or lost on Allen's performance, mainly his arm. Rams are a tough team to run on anyway.