Marilyn became involved in a highly publicized, but short-lived affair with Frank Sinatra and befriended several high-profile personalities during that time, including Peter Lawford, his wife Pat Kennedy, and Pat Newcomb, who became her best friend. The entire group would often spend time together, frequently attending gatherings or large parties at the Lawford and Kennedy homes. The guests were the who's who of Hollywood and at times high government officials would attend, including Robert Kennedy and his brother, then President John Kennedy. It was during these parties that Marilyn and the Kennedy brothers became acquainted during the beginning months of 1962. Kennedy had already dated Monroe, having first met her in early 1946, when he was a Hollywood regular. Kennedy and Monroe according to rumours, dated for a while and then in August of 1947, Fox Studios sent Monroe a telegram informing her that her contract wouldn't be renewed. The word around the studios was that Monroe was dropped by Fox because she was pregnant and John Kennedy was the child's father. Monroe herself said that she gave birth to "a beautiful baby girl" and that she recuperated at the home of John Carroll, who watched over her for Johnny Roselli. Supposedly, New York's powerful Godfather, Vito Genovese, placed Monroe's baby with a Sicilian family in Brooklyn New York, the Maniscalco's and the little girl grew up to become Nancy Maniscalco. She was believed to have had separate affairs with the two men simultaneously. Her relationships with Robert and John, unknown to the public, became the talk of Hollywood. Marilyn was often seen dancing or in intimate conversation at private parties with Bobby or John. According to her closest friends, her heart belonged to the elder brother, John.

At the same time the FBI began to obtain information on Marilyn, which was assimilated into an ever-growing file on her activities. There was also rumour that criminal organizations, such as the Mafia took an interest in Marilyn, especially in her affairs with the Kennedy brothers. Marilyn didn't realize just how deeply involved she was in a very dangerous game with dangerous people.

In 1962, Marilyn moved into a new home, a Mexican style bungalow in Brentwood, California. She purposely moved to be close to the Lawford home and her psychiatrist, Greenson, whom she saw on a daily basis. Marilyn's depression and anxieties began to worsen, despite the therapy. On several occasions she accidentally overdosed on sleeping pills and had to be revived. In fact, her stomach had been pumped for drugs frequently over the last few years. Marilyn became extremely dependent on Dr. Greenson and would continuously consult with him on her increasingly complicated and troublesome life. Taking care of Marilyn became a full-time job for her psychiatrist and he employed a live in companion for her named Eunice Murray.

According to Wolfe, Murray performed many duties for Marilyn including driving her to and from Greenson's home in Santa Monica, receiving visitors and cleaning the house. She also monitored her activities and kept track of her behaviour and moods, which she would report to Greenson daily. Friends of Marilyn found Murray and Greenson to be unusually involved in most aspects of her life. Some believed that Greenson's interests exceeded his professional relationship with the movie star. Others believed that he was after her money. However, these theories were never substantiated. What was known was that Greenson was worried about her affairs, particularly those with the Kennedys. He believed that the liaisons with the two powerful brothers were emotionally damaging to Marilyn and believed they would facilitate her self-destruction.

Earlier that year, Marilyn's relationship peaked with the Kennedys. She was often seen in the company of either John or Bobby Kennedy. It was believed that Bobby fell in love with her, but she did not reciprocate his feelings, although she cared for him deeply and had maintained a sexual relationship with him. Marilyn's friends agreed that her heart was set on winning the affections of John F. Kennedy. He would often visit her at her home or see her at the Lawfords, where they were said to have conducted their affair. John spoke frequently to Marilyn on the phone during the beginning to mid 1962. He even gave her a private number so that she could reach him through the Justice Department. Marilyn's hopes for a future with the president began to soar during this time and she believed that he would someday divorce Jackie Kennedy and marry her.

In April 1962 Marilyn began work on “Something's Got to Give”. It seemed as if her career and life were slowly moving back on track. The following month she performed for John Kennedy at a birthday tribute in his honour at Madison Square Garden. Marilyn emanated sex as she breathlessly sang "Happy Birthday" to the president. It was a performance that sent ripples of gossip through the crowd because her desire for Kennedy was publicly displayed for the first time. The rumours about Marilyn and the Kennedys were beginning to circulate with fury. There was fear that John in particular would be caught up in a whirlwind scandal if his relationship with Marilyn continued at its pace. In the summer of 1962, she had become a security risk and was told to cease all contact with the brothers. The relationships came to an abrupt end and Marilyn was shattered.Lawford, the official Kennedy bearer of bad news to the Hollywood community, called Monroe and told her that she was out, that Kennedy was done with her. "Marilyn, let's face it," he told her, "You're just another of Jack's f***s, so forget about it."

During that time, Marilyn was said to have become severely depressed. She even told several friends that she would come clean about the relationships in retribution for the pain that was inflicted on her by the brothers. But in the weeks just before Marilyn's death, her career and personal life were in a definite upswing. There were a number of new valuable film projects that she was working on and she was very excited about being involved in these films. The weekend before her death, Sinatra and the Kennedy’s lured Marilyn to Lake Tahoe, to make sure she didn’t spill the beans about her affairs with the Kennedy’s. Sinatra and the Kennedy’s plied her to Lake Tahoe with drugs and then took compromising photos of her to be used as blackmail if she threatened to expose the Kennedys. The following weekend Marilyn was found dead in her Brentwood home. Her death appeared to be a suicide resulting from an overdose of sleeping pills. However, there were many who believed that she was murdered because she simply knew too much as there are witnesses that put Peter and RFK at her home the day of her death. The day she died, neighbours saw Bobby and "a man with a doctor's bag" enter her house together. Within four hours she was found dead. Monroe was killed with a barbiturate suppository, but a bottle of oral pills was left at the scene to make it look like a possible suicide. This “man with a doctor’s bag” is believed to have injected Marilyn with the fatal drug that killed her.