This Monday night, the San Francisco 49ers (5-6) hope to reach a .500 winning percentage. The 49ers have struggled after they lost the Super Bowl last season. The Buffalo Bills are standing in their way, though. At 8-3, the Bills are well on their way to an NFL playoff birth. Once they get there, they'll hope to make the AFC Championship Game for the first time in nearly 30 years.The Bills are riding high after they beat the Los Angeles Chargers last week. A win on Monday would all but secure a spot in the playoffs. Josh Allen and company are chasing the Chiefs and the Steelers for AFC seeding. Every game matters, even once they clinch the playoffs. The 49ers are a win outside of the NFC playoff group right now. A victory here would help them stay afloat in this heated race.Monday night's game is set to start at 8:15 p.m. EST. It will be the second leg of a doubleheader after the Washington Football Team face the Pittsburgh Steelers.Four of our last five games are in the national spotlight.@Ticketmaster | #BUFvsSF— Buffalo Bills (@BuffaloBills) December 2, 2020Buffalo Bills vs San Francisco 49ersBetting Odds49ers odds: -1.5 (-118)Bills odds: +1.5 (+100,)Spread: The 49ers are slight -1.5 point favorites against the Bills on Monday Night FootballBuffalo Bills vs. San Francisco 49ersPicks1. The 49ers defense will frustrate Josh Allen more than many defenses he has faced this season. Allen will turn the ball over three times.2. The 49ers will rely on the run, as the Bills will shut down their passing game.3. Broncos quarterback Drew Lock will pass for two touchdowns and over 300 yardsBuffalo Bills vs San Francisco 49ers Key NotesThe 49ers held the Los Angeles Rams to just three first-half points in last week's 23-20 victory The 49ers have relief heavily on RB Raheem Mostert and a platoon of backup runners since Jimmy Garoppolo's injuryHis replacement, QB Nick Mullens was 24/35 for 252 yards last week. The Bills have won only lost one of their last five games. None of these victories have been by more than 10 points.The Bills' only losses this year have come to the Cardinals, Chiefs, and TitansTennessee's 42-16 victory over Buffalo is the Bills' only game this season that was won by more than 10 points.Deebo Samuel: 83 of his 133 yards occurred after contact vs LA RamsMost by a WR in a game this season pic.twitter.com/rKE5JX99QZ— PFF (@PFF) November 30, 2020Buffalo Bills vs San Francisco 49ers Key InjuriesBills:DE Mario Addison (knee) is questionableQB Josh Allen (knee) is probableTE Reggie Gilliam (hamstring) is questionableRB Taiwan Jones (hamstring) is questionable49ers:Note: QB Jimmy Garoppolo and TE George Kittle are not on the injury report. But they remain out with injuriesCB Emmanuel Moseley (hamstring) is questionableWR Deebo Samuel (hamstring) is questionableCB K'Waun Williams (ankle) is questionableBuffalo Bills vs San Francisco 49ers PredictionPrediction: 49ers 28, Bills 26Money line: Bills +100, 49ers -118San Francisco 49ers v Los Angeles Rams