Santo in Suicide Mission aka Misión Suicida opens with a fugitive Nazi scientist named Dr. Muller arriving in Mexico, having been kidnaped in South America by the henchmen of Sebastián. Muller is afraid that a Jewish organization which tracks down war criminals is behind his capture, but Sebastián says no, “as of now you are in the service of the power that defeated Germany and Hitler with the help of the Western powers”. Sebastián runs a training camp for spies and saboteurs in Santo Domingo; he wants Muller to brainwash these people, using a secret Nazi drug. But first, Muller will have to undergo plastic surgery to change his appearance.
Meanwhile, Santo is contacted by Topacio, an agent of Interpol. They want his help in uncovering a spy ring. One of the spies has been caught. “Did he confess anything,” Santo asks. “Nothing. We don’t use torture to extract confessions,” replies Topacio. “Unfortunately, perhaps,” Santo comments. The prisoner had undergone plastic surgery. Soon, the daughter of famous plastic surgeon Dr. Richard Thomas will arrive in Mexico: she will have to be protected. Another Interpol agent is also on the case, code-named “Pisces.”
However, Santo is too late. Miss Thomas is picked up at the airport by Ana Silva, a travel agency employee. Their car is attacked by several men, and Miss Thomas is kidnaped; Ana shoots one of the thugs, but the others escape with their prisoner. Miss Thomas is taken to Sebastián, who says she will be a hostage to force her father to come to Mexico from New York and perform an operation for them. Ana Silva is to be eliminated when she’s found; Miss Thomas says Ana also works as a nightclub performer.
This is the cue for two musical numbers in a club, one by the uniquely-talented Pola Sanders, and the other by Ana. Several of Sebastián’s men force their way into Ana’s dressing room, but she is gone. She goes to Santo’s house and reveals herself as “Pisces.” He will help find Miss Thomas, but first he’s scheduled to wrestle at the arena. Santo and Ana are attacked by more henchmen outside, but escape; after the wrestling match, Santo and Ana are assaulted again; another Interpol agent comes to their assistance and is killed. The spies flee.
The next day, Dr. Thomas arrives in Mexico and is picked up by Sebastián’s men. Santo, driving a cool black Corvette, follows, but a truck cuts him off. A long fight scene follows, and at first Santo is getting a pretty good whupping, but he eventually prevails, and takes one man prisoner. However, the man won’t talk.
Later, more bad guys attack Santo and Ana, but are once more forced to withdraw. This time, one of the henchmen drops a bracelet, inscribed “To Elke with Love, Santo Domingo, October 1971“. While Mexican immigration records are being checked for an “Elke,” Sebastián’s henchman Otto has a bomb planted in Ana’s apartment. They think Santo and Ana are killed in the ensuing explosion. Topacio says an Elke Baumann came to Mexico from South America, a notorious hideout for former Nazis. She currently resides in Santo Domingo, where she runs a gym for women. Meanwhile, Dr. Thomas operates on Muller, but the Nazi scientist will have to keep his bandages on for about two weeks before he can expose his “new” face.
Santo and Ana go to the Dominican Republic. Ana signs up for classes at Elke’s training academy, proving her ability by defeating Debbie, one of Elke’s karate instructors. However, Elke is suspicious of Ana’s proficiency. That night, Santo sneaks into Elke’s office; he spots a photo album with a large swastika on the cover, and steals a photo. After knocking out a guard, he makes his escape despite pursuit by armed female commandos. Topacio identifies the man in the photo as Sebastián, a former officer in Hitler’s guard; after the defeat of Germany, Sebastián blamed the U.S. and joined forces with the Russians. He is the head of ring that sends spies and saboteurs to the United States. However, Interpol can’t do anything until Santo makes sure Dr. Thomas and his daughter are safe, and Sebastián is located. Otto and Elke are afraid to tell Sebastián what has occurred.
Debbie, who is Otto’s sister, warns Ana not to ask so many questions about the operation, but it’s too late: Elke and Otto take Ana prisoner. Santo arrives but is captured as well. He escapes by diving into the swimming pool, defeating the resident shark, and swimming through a tunnel which eventually winds up in a creek somewhere .
Meanwhile, Debbie helps Ana escape. Debbie says her parents were killed in the bombing of Berlin in 1945, which made Otto hate the USA. Debbie, who was very young at the time, doesn’t have Nazi sympathies. Driving a gold Corvette, she helps Santo and Ana get back into the spies’ compound. Santo defeats two male karatecas, and bursts into the room where Sebastián, Otto, Elke, Dr. Thomas, Miss Thomas, etc., are ready for the unveiling of Muller. A fight breaks out. In a ludicrous scene, Sebastián and one of his henchmen shoot each other (when Santo, who is between them, suddenly drops to the floor)! Interpol agents break in and arrest everyone else. Muller’s face is revealed: he looks a little younger, but the real difference is a big swastika carved into his forehead by Dr. Thomas! Thomas said, even at the risk of his own life and that of his daughter, he wanted to mark the Nazi forever.
Ana goes looking for Santo, whom she has a crush on. But she only finds his mask, inscribed “To Ana, with love.”