Born on Mars Colony, Tarses had long been interested in serving in Starfleet, but had decided to enlist as a normal crewman rather than applying for the Academy, as he doubted his ability to cope with the pressure of Starfleet Academy. He eventually enlisted, serving as a medical technician at several outposts before stardate 43587 when he was assigned to the USS Enterprise-D under Doctor Beverly Crusher.
In 2367, an explosion in the Enterprise-D's warp core led investigators to discover that J'Dan, a Klingon exchange officer on board the ship, had been involved in smuggling secrets to the Romulans. J'Dan admitted to his espionage, and hinted that there were co-conspirators on board the Enterprise-D as well.
Tarses, who occasionally administered a medicinal hyposyringe to the Klingon traitor, was extensively questioned by a Starfleet board of inquiry. After initial questioning, the scope of the inquiry was widened. This was due to Admiral Norah Satie's Betazoid aide sensing that he was hiding a secret. When questioning continued, Commander William T. Riker was assigned as his legal counsel for his "own protection". During questioning, Simon was confronted with evidence that proved that he was a quarter Romulan and not a quarter Vulcan, as he had falsely claimed on his Starfleet entrance application.
Commander Riker quickly advised him via a whisper in his ear to invoke his right against self incrimination which he did. His falsehood threatened to end his Starfleet career, although Captain Jean-Luc Picard, after having gotten to know Simon personally, spoke in Tarses' defense when he was later put on trial himself, arguing that Tarses' only crime was concealing his Romulan heritage and he had done no other harm. (TNG: "The Drumhead")
"This hearing is convened on Stardate 44780 as a continuing inquiry into the activities of Crewman Simon Tarses. Mister Tarses, for your own protection, I have assigned a counsel to you in the person of Commander William Riker."
"Thank you, sir, but I don't need protection. I have not done anything wrong."
- - Jean-Luc Picard and Simon Tarses
"Isn't it true that the paternal grandfather of whom you speak was not a Vulcan but was in fact a Romulan? That it is Romulan blood you carry and a Romulan heritage that you honor?"
(William Riker whispers in Simon's ear)
"We're waiting, Mister Tarses."
"On the advice of my counsel I refuse to answer that question, in that the answer may serve to incriminate me."
- - Sabin Genestra and Simon Tarses
"Tell me a little about yourself, Crewman. I know you were born on Mars Colony."
"Yes, sir. All my life I wanted to be in Starfleet. I went to the Academy's training program for enlisted personnel. I took training as a medical technician and I served at several outposts. The day that I was posted to the Enterprise was the happiest day of my life."
- - Jean-Luc Picard and Simon Tarses
"You didn't do it. (Apply to become an officer)"
"No. I was eighteen, and eager. The last thing I wanted to do was spend four years sitting in classrooms. I wanted to be out there, traveling the stars. I didn't want to wait for anything. And now it's done, isn't it? My career in Starfleet is finished."
"Not if you aren't guilty, Simon."
"It doesn't matter. I lied on my application, and that mistake will be with me for the rest of my life."
- - Jean-Luc Picard and Simon Tarses
The script for "The Drumhead" describes Tarses as simply "a mild-figured humanoid." 
This episode established in dialogue that Tarses was an enlisted crewman who had not gone to the Starfleet Academy; therefore, he wore a blank collar. This lack of rank insignia for crewmen and non-commissioned officers was used throughout Star Trek: Deep Space Nine and Star Trek: Voyager, although chief petty officers were assigned different insignia.
It was not revealed what punishment, if any, Tarses might receive for lying in his documentation. After Tarses says this incident might mean "the end of his career", Picard reassures him that is not the case if he is found not guilty. Tarsis says that it doesn't matter, since lying on his application will follow him the rest of his life.
Simon Tarses has appeared in a number of non-canon works.
The Star Trek: The Next Generation novel, Infiltrator, set in 2370, mentions that Tarses' career was over as a result of lying about his bloodlines. Star Trek: Starship Creator and later novels (see below) ignore this reference.
Simon Tarses appears as a selectable crew member in the video game Star Trek: Starship Creator, in which his computer record states he is the son of Marya and Tarvek Tarses and was born on the Martian Colonies in the year 2344 and his brother is named Joseph. The personnel file goes on to say that he attended a special training course for enlisted personnel as his reason for attending Starfleet Academy and, following the completion of his training as a medical technician in 2363, he was posted to an infirmary on Outpost Sierra VI. After several months on Sierra VI, it says Tarses then transferred to the infirmary on Outpost Seran T-1. Following a year at Seran T-1, Tarses transferred to the medical facility on Ivor Prime in 2365, and under the direction of Doctor Lu Chen Chow, he assisted in isolating an alien prion pathogen that had caused an outbreak of transmissible spongiform encephalopathy on Icor IX. As a reward for his assistance, Tarses was promoted to crewman first class. After the events of "The Drumhead", Tarses received a six-month suspension before going back to work. Shortly after, on encouragement by Captain Picard, Tarses enrolled at Starfleet Academy and in 2372, graduated with the rank of Lieutenant. He was then assigned to the USS Enterprise-E as a nurse.
Lieutenant Tarses appears in the novel Do Comets Dream?, set in 2371, where he becomes romantically involved with a Thanetian, after helping to save her world from destruction by a collision with an artificial comet.
In the Pocket DS9 two-part relaunch novel Avatar, set in 2376, Doctor Simon Tarses is assigned to Deep Space 9 under Julian Bashir, who leaves him in charge of the station's Infirmary while Bashir conducts a three-month mission in the Gamma Quadrant aboard the USS Defiant in Star Trek: Deep Space Nine - Mission Gamma.
Tarses appears again in the Deep Space Nine novel Warpath, set in 2377, where he develops an innovative treatment involving nano-technology, genetronic replication, and cybernetic regeneration that repairs the injured spine of Lieutenant Ro Laren after she is brutally assaulted by a rogue Jem'Hadar observer named Taran'atar. In Fearful Symmetry, Tarses is responsible for Ro's physiotherapy during her recuperation.
According to the Star Trek: Destiny novel Gods of Night, Tarses is assigned as chief medical officer on the USS Aventine under Captain Ezri Dax in 2381. While the Aventine is investigating the wreck of the NX-02 Columbia, Doctor Tarses and a medical team have to investigate the horrific deaths of two engineering crew members, Yott and Komer, who had been killed for sustenance by a member of the Caeliar species, who had hidden aboard the wreck for almost two hundred years. Although the scene is gruesome, Tarses learned at medical school to suppress his gag reflex while operating on cadavers. He also leads the medical team that performs the investigation on a third death in the shuttle bay of the Aventine, determining them to be related.