Titans vs. 49ers Odds & Betting Predictions - December 14, 2025

The poor Titans are now 0-10 against current top-eight seeds, losing by an average of 14.9 PPG. They're 2-1 in all other games, but it's another tough game here with the 49ers coming off their bye and looking like they should be able to name their score. A Christian McCaffrey touchdown feels like a free space. The Titans have allowed 14 rushing touchdowns, third most in the NFL, with at least one TD to all but three opposing RB1s. McCaffrey has at least one touchdown in 9-of-13 games, but at -275 for an Anytime TD, the juice may not be worth the squeeze. I'll jump straight to 2+TDs at +170 (bet365). McCaffrey has at least two scores in three of the last five 49ers wins. He's become this entire offense. Touch 3+ TDs at +650 too. If McCaffrey does have another big game against these Titans, he could find himself in the mix for Offensive Player of the Year. I wrote in the Extra Point in this week's Pick Six about why I'm betting McCaffrey at +2500 to win OPOY too (FanDuel).

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Niners off the bye…Minor travel advantage with a central time-zone team flying out west. Robert Saleh with extra time to prep for Cam Ward who has been awful this season. He was outplayed by Shedeur Sanders last week, albeit in a win. 49ers #2 in 3rd down conversion %...#2 on special teams…they have been so much better this season than many of us have given them credit for. I know laying big numbers in the NFL is a tough pill to swallow, but I think the Niners are worth the plunge.