The 36-year-old came off with an unspecified injury in the first half of Saturday's loss to Poland, which has left Mexico at the bottom of the standings with just one point to their name.
Guardado's issue is believed to be muscle-related, but there is currently no indication as to how severe his problem is, although Martino is still well-stocked when it comes to engine room options.
Ajax's Edson Alvarez was dropped to the bench at the weekend but should now be in with a good chance of coming back in with Guardado potentially absent, although Erick Gutierrez was chosen to replace the Real Betis man.
Alvarez may nonetheless be preferred alongside Hector Herrera and Luis Chavez in the engine room, and Martino could also elect to switch to a back four with his side in desperate need of goals.
Nestor Araujo could be the unlucky defender sacrificed if that is the case, as Guillermo Ochoa continues to be protected by Hector Moreno and Cesar Montes.
Up front, Hirving Lozano and Alexis Vega could be providing support to a new presence in Raul Jimenez, who may finally be deemed fit enough to start as he bids to win his 100th cap for El Tri.
Mexico possible starting lineup: Ochoa; Sanchez, Moreno, Montes, Gallardo; Herrera, Alvarez, Chavez; Lozano, Jimenez, Vega