Kyle Shanahan and the San Francisco 49ers (8-6) will visit Mike Vrabel and the Tennessee Titans (9-5) on Thursday Night Football. This matchup features a top-10 rushing attack against a top-five run defense. San Francisco is seventh in rushing yards per game (126.6). On the other sideline, Tennessee is second in rushing yards allowed per game (86.9). 

Kickoff from Nissan Stadium is set for 8:20 p.m. ET. San Francisco is favored by 3.5 points in the latest 49ers vs. Titans odds from Caesars Sportsbook, while the over-under is set at 45.5. Before locking in any Titans vs. 49ers picks, be sure to check out the NFL predictions and betting advice from the SportsLine Projection Model.

The model, which simulates every NFL game 10,000 times, is up over $7,000 for $100 players on top-rated NFL picks since its inception six-plus years ago. The model enters Week 16 of the 2021 season on an incredible 133-96 run on top-rated NFL picks that dates back to the 2017 season.

The model also ranked in the top 10 on NFLPickWatch four of the past five years on straight-up NFL picks and beat more than 94 percent of CBS Sports Football Pick'em players four times during that span. Anyone who has followed it is way up!

Now, the model has simulated 49ers vs. Titans 10,000 times and just revealed its coveted NFL picks and predictions. You can head to SportsLine now to see the model's picks. Here are several NFL odds and betting lines for Titans vs. 49ers:

  • 49ers vs. Titans spread: San Francisco -3.5
  • 49ers vs. Titans over-under: 45.5 points 
  • 49ers vs. Titans money line: San Francisco -180, Tennessee +155 
  • SF: 49ers are 7-7 against the spread this season
  • TEN: Titans are 8-6 against the spread this season

Why the 49ers can cover

San Francisco trots out a top-10 defensive unit. The Niners are sixth in the NFL and allow 322.8 total yards per game. Teams have struggled to pass the ball against the 49ers, who rank sixth in passing yards allowed per game (213.2). Over the past six weeks, San Francisco has held three of its opponents to fewer than 300 total yards.

In the Week 10 matchup against their division rival Los Angeles Rams, the 49ers limited a high-powered offense to just 278 total yards. Quarterback Matthew Stafford threw two interceptions, while the Rams only ran for 53 yards. The Jacksonville Jaguars didn't have much luck the following week against this unit and finished with just 200 total yards of offense. The 49ers' defense has found its groove the past few weeks and will try to stack up dominant performances right in time for playoffs. 

Why the Titans can cover

Tennessee has defended the run extremely well this year. The Titans are second in the NFL against the run, allowing just 86.9 rushing yards per game with just 3.9 yards per carry. Edge rusher Harold Landry is also having an excellent season. The Boston College product is third on the team in tackles (65), first in tackles for loss (13) and first in sacks (11). 

Landry has registered a sack in eight games thus far, including back-to-back two-sack performances against the Jacksonville Jaguars and Buffalo Bills. Defensive tackle Jeffery Simmons has been an anchor in the middle of the Titans' defense. He has recorded 50 total stops to go along with 11 tackles for loss and 7.5 sacks. Defensive lineman Denico Autry has also generated pressure this year and currently has seven sacks. Tennessee's front four will look to impose their will against the 49ers' offensive line. 

How to make 49ers vs. Titans picks

SportsLine's model is leaning over on the point total, projecting the teams to combine for 46 points. The model also says one side of the spread has all the value. You can only see the model's 49ers vs. Titans pick at SportsLine

So who wins Titans vs. 49ers on Thursday Night Football? And which side of the spread has all the value? Visit SportsLine now to see which side of the Titans vs. 49ers spread to jump on, all from the advanced model that is up over $7,000 on its NFL picks, and find out.