Khan has his eyes firmly set on Vargas tonight, as the two lock horns in front of 8,000 fans in Birmingham.
But should the Brit win, he is expected to fight either Manny Pacquiao or Kell Brook in his next bout.
Vargas sees this as an opportunity to shock the second city, with Betfair making the Columbian a 10/1 underdog.
Prior to the fight, Vargas vouched to punish the 31-year-old: “He’s an old man. He’s been hurt before and he’s been stopped many times.
“I just have to land one punch on his chin, left or right hand. His feet will go all over the place and if he’s still there I’ll hit him again and again.”
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The chief support is a rematch between Jason Welborn and Tommy Langford for the British middleweight title.
Welborn won the exhilarating clash via split decision in May, in a Fight of The Year contender.
Meanwhile, local boy, Sam Eggington takes on Tanzanian Hassan Mwankinyo, the Brummie re-inventing himself at 154.
Amir Khan v Samuel Vargas results
Undercard:
Steven Donnelly beats Miguel Aguilar on points
Sean McComb beats Lesther Cantillano via KO
Osman Aslam beats Jack Summers via TKO
Qais Ashfaq beats Gary Austin via KO
Kieron Conway v Gino Kanters
Shakan Pitters v Imantas Davidaitis
Gamal Yafai v Brayan Mairena
Ryan Kelly v Kelcie Ball
Scott Fitzgerald v Craig Morris
Lewis Ritson v Oscar Amador
Sam Egginton v Hassan Mwakinyo
Jason Welborn v Tommy Langford