The 60-year-old guided the Seleccao to a 1-0 victory over Gerardo Martino's side in an international friendly in November 2014, with Raphael Guerreiro's strike in second-half stoppage time settling the fixture.
Since then, Argentina have gone eight games without defeat, only failing to win in their Copa opener against Paraguay in La Serena, while they advanced past Colombia in the quarter-finals on penalties following a 0-0 draw.
Being last the coach to get the better of the South American giants, he was asked for his thoughts on how Chile could go about doing the same in the showpiece event on July 4.
"Argentina is a very strong opponent, they have great players. To win, you have to play the perfect match and have a little luck," Santos told El Mercurio.
He believes that the key to playing the perfect match lies in not focusing all attentions on Albiceleste captain Lionel Messi.
The 28-year-old has only scored one goal so far in Chile but was impressive in Argentina's semi-final with Paraguay - providing three assists.
"You cannot mark [Messi] man to man, because the only thing you gain is a problem. He is so good that he always finds a way of having more freedom," Santos added.
"It is better to use zonal marking ... you have to prevent him from receiving the ball."