Simon Tam was born on Osiris in late November circa 2490 to parents Gabriel and Regan Tam. Along with his sister River, he was raised with a great deal of privilege, never wanting for anything. He atteneded the top medical academy (MedAcad) on Osiris, graduating in the top 3% of his class. He completed his residency in eight months rather than three years and became a trauma surgeon at a hospial in Capital City, Osiris.
His sister River was invited to attend an Alliance sponsored Academy and though the Tam's had never heard of it, River wanted to badly to go they allowed it. They received letters at first but soon the letters became more and more sporadic. The letters began making less and less sense and Simon soon figured out there was a code in them - "They're hurting us." His parents refused to believe anything was wrong so Simon made it his mission to help River and rescue her from the Academy. It took him two years and all the money he had before he was contacted by a group of men from an underground movement who told him where River was. Simon rescued her and cryogenically froze her in a box. On Persephone he sought discreet transport and that is how he came to Serenity, captained by Malcolm Reynolds.
Simon initially hid River from the crew of Serenity but when a federal agent came on board, Malcolm Reynolds went looking to Simon for answers. Simon explained his situation with River, telling the crew that they were now on the run and wanted fugitives and that he didn't know what had been done to River at the Academy. Simon soon became part of the crew as a medic while he performed tests on River to figure out what was done to her. He developed a close relationship with the ship's mechanic, Kaylee Frye.
Simon went to the crew of Serenity asking them to help sneak he and River into the diagnostic ward of a hospital on Ariel, which he could use to see what happened to River. He discovered that her brain had been lobotomized several times and she'd been stripped of part of it. After the events on Ariel, where Simon, River and Jayne are nearly captured by the Feds, Simon becomes a bit lessput together and begins to relax more with the crew. He takes part in a mission to rescue the Captain when he is kidnapped and the crew even accepts him more.
Simon is shot in the leg when trying to keep a bounty hunter named Jubal Early from taking River. When Mal begins taking River on jobs, putting her in danger, Simon protests and eventually decides he and River need to leave Serenity. They stay, however, when River all of a sudden begins to attack people in a bar, raising suspicion. They learn that the Alliance trained her not only to be psychic but an assassin as well. She begins to talk about Miranda, which the crew discovers is a planet. On Miranda they find out that the Alliance inadvertently created Reavers, something River knew and that contributed to her schizophrenia. The crew makes it their mission to make sure the universe knows what the Alliance did and has to battle with Reavers to reach their goal. Simon is wounded in the stomach when he realizes he's left his medical bag behind. River runs to save him, taking her turn as he has constantly been taking care of her. With the truth about Miranda and the Reavers out, Simon pursues his relationship with Kaylee.
Simon was played throughout the show and the movie by Sean Maher. In flashbacks in the episode "Safe" he was played by Zac Efron.