Danny Welbeck left the club to join Arsenal in a £16 million transfer while Javier Hernandez also departed to join Real Madrid on a season-long loan deal.
Their deadline day activity leaves Van Gaal with three striking options rather than four, and although he has three world class options up to to choose from, it will surely be a risk to continue to play two up top.
Robin Van Persie and Falcao have ongoing fitness concerns and will both be hoping to put injury-hit campaigns behind them this season.
Club captain Wayne Rooney is the other option in attack and he will expect to play every game, but may drop back into a slightly deeper position once more.
Team's with just three strikers to choose from usually utilise one option at a time and field a lone striker and United may be set to do just that.
Playing two together increases the risk that one, or both strikers pick up injuries and that would instantly leave Van Gaal short of options.
The Dutchman has been trying to get his 3-5-2 formation to work since taking over, but United have yet to win in three Premier League games so far, and he may now look to switch to a more familiar set-up.
A 4-3-3 system would be ideal for the Red Devils, as would a 4-2-3-1 set-up as this would allow creative players to have more of an influence on the game.
Van Gaal must try and fit in Ander Herrera, Juan Mata, Angel Di Maria and Wayne Rooney as well as choosing between Falcao and Van Persie on a weekly basis.
He may stick to his guns and keep his 3-5-2 formation but United would surely thrive from a more traditional set-up, and with just three striking options now at the club, it would be wise to field one lone striker at a time.