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The last chance to make a Week 16 NFL SGP comes on 'Monday Night Football' as the San Francisco 49ers visit the Indianapolis Colts at 8:15 p.m. ET. Both teams are on streaks, as San Fran has won four straight, while Indy has lost four straight. That would make NFL picks on the money line in favor of the Niners attractive for a 'Monday Night Football' SGP, but the recent history of this matchup may suggest otherwise. The Colts have won five straight games versus the Niners, so your MNF same-game parlay may want to consider NFL props, spread picks and the over/under.

While this game features the likes of Christian McCaffrey, Jonathan Taylor and George Kittle, many will target 44-year-old Philip Rivers with prop bets for their MNF SGP. After 120 passing yards last week, Rivers' O/U for passing yards is 158.5 for Monday. San Fran's defense isn't the same caliber as the one in Seattle that Rivers saw last Sunday, so the Over could be appealing for your NFL same-game parlay. Before locking in any Colts vs. 49ers picks for your 'Monday Night Football' SGP, be sure to see the 49ers vs. Colts prop predictions powered by SportsLine's Machine Learning AI.

New users can target the DraftKings promo code, which offers $200 in bonus bets if your bet wins to bet on props like Jonathan Taylor as an anytime touchdown scorer:

Built using cutting-edge artificial intelligence and machine learning techniques by SportsLine's Data Science team, AI Predictions and AI Ratings are generated for each player prop. 

Now, the model has analyzed Colts vs. 49ers on 'Monday Night Football' and locked in three confident best bets for an NFL SGP. If you successfully parlay its picks, you'd be looking at a payout of well over 6-1. You can only see the Machine Learning Model player prop predictions for San Francisco vs. Indianapolis here.

Top Monday Night Football SGP picks

After simulating 49ers vs. Colts, SportsLine AI says Niners running back Christian McCaffrey goes Under 17.5 carries (+102). With the postseason in their sights, the Niners are giving backup, Brian Robinson Jr., more touches in order to keep McCaffrey fresh for the playoffs. The former Commander has at least seven carries in each of his last five games, after reaching that number just twice over his first nine contests. Additionally, Indy's defensive strengths and weaknesses may have San Francisco lean on McCaffrey more thru the air than on the ground.

The Colts have the No. 6 run defense and have allowed the second-fewest rushing touchdowns in 2025. On the other hand, the Colts have the second-worst pass defense, and San Fran will need more out of McCaffrey through the air with Ricky Pearsall (knee/ankle) out. McCaffrey is projected to have 14.4 carries on average, as this NFL prop rated 4.5 stars could be a part of a winning 'Monday Night Football' SGP. See which other MNF same-game parlay picks to make here.

Bet McCaffrey to go Under 17.5 carries at DraftKings:

How to make Colts vs. 49ers SGP picks

In addition, the SportsLine Machine Learning Model has six other NFL props that are rated 4 stars or better that could be a part of your 49ers vs. Colts SGP picks. You can only see the Machine Learning Model's Monday Night Football NFL parlay at SportsLine.

What are the model's top same-game parlay picks you should target with your Colts vs. 49ers predictions? Visit SportsLine now to see the Monday Night Football SGP from the SportsLine Machine Learning Model and find out.