Squirrel’s Nuts & Bolts 49ers – Colts MNF Showdown Strategy (Week 16 NFL DFS)

Dec 22, 2025

Kevin Ng-Imagn Images

Week 16 of the NFL season wraps up with an interconference showdown as the 49ers travel to Indianapolis to face the Colts. Both teams are currently in the playoff race but going in different directions – the 49ers have won four games in a row while the Colts have lost four games in a row. San Francisco enters as a 5.5-point road favorite, with the total set at 45.5 points.

The 49ers’ offense has battled injuries for much of the season, but still ranks 10^th in the league in yards and points per game. Brock Purdy, Jauan Jennings, George Kittle, and Ricky Pearsall have all missed multiple games, but all except Pearsall are expected to play Monday Night. Christian McCaffrey continues to anchor the attack, leading the team in both rushing and receiving yards while ranking eighth in the NFL in receptions. Jennings (495 receiving yards), Kittle (484 receiving yards), and Kendrick Bourne (499 receiving yards) are all healthy for this game and should make up the bulk of the San Francisco offense after McCaffrey.

The Colts’ offense has fallen apart with the team losing their top three quarterbacks in recent weeks and calling 44-year-old Philip Rivers out of retirement. In his first game since the 2020 season last week, Rivers threw for 120 yards and a touchdown, while Jonathan Taylor carried the ball 25 times for 87 yards. Taylor should continue to have a heavy workload while the Colts focus on a short passing game to Michael Pittman, Tyler Warren, and Alec Pierce.

This matchup features two teams going in different directions but fighting for playoff positioning. Let’s break down this interconference showdown, highlight the key plays, and uncover the strategies that could help you climb the leaderboards.