Sheldon and Amy struggle to choose a best man and maid of honor from their friends. They secretly decide to test and score them, allowing everyone to have an equal shot at either role. Once the gang finds out, none of them apart from Bernadette and Stuart want to be in the wedding. Sheldon settles for Stuart as best man but, once Leonard tells Sheldon that, as the groom, the decision is his alone, he picks Leonard. Amy is set to call Bernadette but, once Penny realizes Amy is her best friend, she immediately pitches herself for the position and Amy enthusiastically chooses her. Amy later makes Penny tell Bernadette the bad news.
Sheldon's childhood friend from Texas, Tam, is visiting the university with his son. Sheldon does not want to see him and the others wonder why Sheldon has never mentioned Tam. Tam is unaware Sheldon is angry with him, thinking they just naturally drifted apart. Sheldon's brother George does not know the reason either. Sheldon eventually reveals Tam promised he would move to California with Sheldon, but then got a girlfriend and stayed with her, leaving Sheldon feeling abandoned. Tam and Sheldon make up and Sheldon has Leonard take Tam to the airport. Meanwhile, Penny and Bernadette want to get to know Anu, impressed by her connections in the hotel industry. They tell her embarrassing things about Raj and wonder if they can go out with her again after Raj confronts them.
However, no legal action was required to end production of the other show: as soon as it became known that the show was unlicensed, the actors quit and the producers canceled it. Dmitriy Tankovich (who plays Leonard's counterpart, "Seva") said in an interview, "I'm upset. At first, the actors were told all legal issues were resolved. We didn't know it wasn't the case, so when the creators of The Big Bang Theory started talking about the show, I was embarrassed. I can't understand why our people first do, and then think. I consider this to be the rock bottom of my career. And I don't want to take part in a stolen show".
Getting called into Human Resources for Amy's outburst, Mrs. Davis tells her and Sheldon they are blowing their chances at the Nobel Prize. Amy would be the fourth woman to win in Physics, pressuring her to be a role model for women everywhere. To calm down, they try a sensory deprivation tank, which Sheldon loves, but Amy's mood only worsens. Sheldon does not know how to help and ends up holding her while singing "Soft Kitty". A newly confident Amy goes back to Human Resources to be allowed to campaign again and shares a drink with Mrs. Davis. Meanwhile, Howard buys a scooter to ride with Raj like in the old days. Bernadette finds out and makes him sell it since it's too dangerous. Bert buys it and ends up meeting a nurse after he dislocates his arm in a wreck.
As the theme of the show revolves around science, many distinguished and high-profile scientists have appeared as guest stars on the show. Famous astrophysicist and Nobel laureate George Smoot had a cameo appearance in the second season. Theoretical physicist Brian Greene appeared in the fourth season, as well as astrophysicist, science populizer, and physics outreach specialist Neil deGrasse Tyson, who also appeared in the twelfth season.
Raj hooks up with a recently separated woman, Nell, after one of his lectures at the planetarium. Her husband, Oliver, confronts Raj at the planetarium and then breaks down over the end of his marriage. After comforting Oliver, Raj talks to Nell and convinces her to give her husband another chance. Meanwhile, after diving once again into string theory and sprawling his work across his and Amy's apartment, Sheldon approaches a reluctant Leonard and Penny and convinces them to let him use his old room to study for a three-day trial period with an agreement to be quiet and stay out of their way. Sheldon surprisingly sticks to this agreement, being a reasonably good guest, which shockingly frustrates Leonard to no end. After Leonard lets out his frustrations, Sheldon then renegotiates the guest tenancy agreement for an extra few days and resumes being his normal demanding self, much to Leonard's relief.
Sheldon is annoyed that Amy does not have time to work on the super-asymmetry project with him so he talks President Siebert into getting her removed from her own project at the university. Amy is angry at both of them as she wants to still have her own identity outside the marriage. When confronted by Amy, Siebert apologizes to her but states that it will be difficult for the university to give her her project back. After talking with Arthur Jeffries in a dream, Sheldon apologizes to Amy and both of them talk about their fears in their marriage. Meanwhile, Raj does not want to have Howard join him in his show at the planetarium, thinking he'd just use his astronaut status to make it about himself. Raj eventually lets him join in and Raj and Howard spend the whole time complimenting each other, surprising Bernadette, Leonard and Penny.
While Jim Parsons was the one who'd had enough with The Big Bang Theory, opting not to renew his contract to play socially awkward theoretical physicist Sheldon Cooper and bringing about the demise of the show in the process, he won't be escaping the show's orbit entirely. He's still attached as both executive producer and narrator of prequel series Young Sheldon, returning for a third season on CBS this fall. "There was no factor; there was no situation that I was like, 'Well, I've had enough of that.' No. There was nothing like that. It was just…when you know, you know," he explained to The Hollywood Reporter in mid-May.
Sheldon needs half a billion dollars to prove his latest concept of string theory, which the University cannot afford to fund. Crowdfunding and selling some of his most valuable comic books to Stuart give him a small start. When Raj mentions gambling in Las Vegas, Sheldon goes there but is caught calculating odds by security before he can make any bets. Meanwhile, Amy takes Penny and Bernadette shopping for her wedding dress. She loves an old-fashioned one that the other girls admit that they find ugly, though Penny assures Amy she can make her own decisions about her wedding. Sheldon, however, comes home and sees Amy in the dress and loves how she looks.