Sabrina Santiago came to Port Charles and joined the nursing staff at the hospital after her cousin, former resident Juan Santiago, had spoken highly about the town and the hospital. Sabrina had been raised by her cousin's family after her mother's death when she was young. Her mother had been a nurse and Sabrina planned to follow in her footsteps. At General Hospital, Sabrina immediately developed a crush on neurosurgeon Patrick Drake. She was intrigued by him after she learned he was recently widowed and raising his young daughter on his own. Sabrina was honored when Patrick reached out to her and mistakenly believed that he wanted to take her on a date. Instead, Patrick asked Sabrina to baby-sit his daughter Emma while he went out on a date with a fellow doctor named Britt Westbourne.

Britt and Sabrina each sensed the other woman's interest in Patrick and Britt showed her superiority as a doctor by ordering Sabrina around. Regardless, Sabrina agreed to watch Patrick's daughter and she enjoyed spending time with Emma in Patrick's home. As Sabrina and Emma bonded, Patrick and Sabrina started to develop a friendship, much to Britt's dismay.

Sabrina remained intrigued by Patrick's former wife Robin and Emma told Sabrina about the Nurses Ball that the hospital used to hold to raise money for HIV after Robin was declared HIV positive. Sabrina decided to resurrect the Nurses Ball as a tribute to Robin. Her friends Elizabeth Webber and Felix Dubois joined the effort, along with Patrick, Elizabeth's brother Steve, and Britt. They struggled to find funding for the ball until Felix connected Sabrina with Lucy Coe.

As the plans for the ball moved forward, Sabrina continued to spend time with Patrick's daughter and Patrick as well. They almost shared a kiss but Sabrina distanced herself from Patrick and Emma after Britt led Sabrina to believe that Patrick knew about her crush and felt uncomfortable around her. Sabrina tried to avoid Patrick even though Felix and Elizabeth urged her to fight for him. Eventually Patrick ended his relationship with Britt. She blamed Sabrina for the break-up and took steps to end Sabrina's nursing career before it officially started. Patrick remained by Sabrina's side while she fought to save her career.

After Patrick's unwavering support, Sabrina confessed her feelings for him. When Patrick did not immediately express the same feelings, Sabrina decided to move on and accepted a date with Milo Giambetti. As Sabrina and Milo got to know one another, Patrick realized that he had romantic feelings for Sabrina and escorted her to the Nurses Ball.

Sabrina was unsure of where she stood with Patrick after Britt announced at the ball that she was pregnant with Patrick's child. Despite Britt's news, Sabrina and Patrick decided to pursue a relationship. Sabrina felt that Britt planned to use the pregnancy to win Patrick back. With the help of her roommate Felix, Sabrina chose to fight for Patrick by allowing Britt to move in with them after Britt claimed to have complications with the pregnancy. As Britt's pregnancy progressed, Sabrina and Felix questioned the paternity of Britt's child until test results confirmed that Patrick was the child's father. Sabrina remained by Patrick's side and supported his decision to be a part of his child's life.

Eventually Britt confessed that Patrick was not her baby's father and Patrick and Sabrina were able to move forward with their relationship without Britt's interference. However, Sabrina's former lover Carlos arrived in Port Charles and claimed that he still loved Sabrina and wanted her back. Carlos questioned Sabrina's place in Patrick's life since Patrick still wore his wedding ring and had not made a formal commitment to her. She defended Patrick but secretly wondered if he would ever be ready to move forward. Her worries ceased after Patrick proposed marriage and they made plans to marry as soon as possible.

Sabrina's plans for a happy future with Patrick and Emma were interrupted as Patrick and Sabrina exchanged wedding vows. Patrick's wife Robin arrived at the church and Sabrina was forced to watch Patrick and Robin reunite with a passionate kiss. The wedding never resumed and Sabrina ran off. She spent an intoxicated evening with Carlos although he swore they had spent the night in a platonic manner. Later, Patrick spoke with Sabrina and asked for her patience as he sorted out his feelings for both women. After weeks of uncertainty, Patrick informed Sabrina that he belonged with Robin but assured Sabrina that he did truly care for her.

As Sabrina dealt with a broken heart, Carlos turned to her for safety after he had been shot. She allowed him to hide from the mob at her apartment and she realized that she was pregnant with Patrick's child. Felix encouraged Sabrina to tell Patrick but she feared that he would accuse her of using the pregnancy to undermine his relationship with Robin. Although Sabrina had not asked, Carlos stepped in and announced that he was the father of Sabrina's child. She went along with the lie but later confessed the truth to Patrick. He promised to be involved in his child's life but was distracted after Robin left Port Charles. Sabrina hoped that her pregnancy had not caused Robin to leave.

Sabrina accepted that Patrick was not able to be involved with her pregnancy while he dealt with Robin's absence. She continued to reach out to him and he accompanied her to an appointment in which they learned that they were having a son. Both Sabrina and Patrick were overjoyed and they shared the news with Emma. They were together when a car crossed into their lane and forced them off the road. Patrick and Emma were fine but Sabrina briefly lost consciousness and went into premature labor which forced her to deliver her son on the side of the road. The baby was in critical condition when they arrived at the hospital and Patrick and Sabrina prayed that he would survive. After their son grew stronger, they named his Gabriel Drake to honor Sabrina's mother and the new child's connection to Emma.

Although Gabriel's condition appeared to be improving, he developed a fatal infection. Patrick and Sabrina were present during their son's final heartbeat which Sabrina listened to using her mother's stethoscope. Sabrina struggled to accept her son's death and briefly believed that she was about to exchange nuptials with Patrick. Felix was concerned about Sabrina and he reached out to her cousin Juan. With Patrick's encouragement, Sabrina decided to spend some time with Juan in Puerto Rico. She left with him after Gabriel's funeral.

When Sabrina returned to Port Charles, she was shocked to learn that Rafe Kovich had been instructed to run Patrick's car off the road. She vowed to avenge her son's death and paid Carlos a visit in prison. He revealed that Ava Jerome had threatened to harm Sabrina if Carlos did not confess to the murder of A.J. Quartermaine. Sabrina believed that Ava was to blame and decided that Ava and her unborn child should suffer. Sabrina switched Ava's medication with one that would cause premature labor and she anxiously awaited Ava's arrival at the hospital. When Patrick uncovered evidence that pointed to another suspect, Sabrina regretted her actions and tried to prevent Ava from consuming any more of the harmful substance.

After Sabrina confessed what she had done to Ava, she was fired from her nursing position at the hospital. While she contemplated her next move, she was relieved to learn that Carlos was no longer serving prison time for a crime he did not commit. Sabrina was hesitant to believe that Carlos planned to leave the mob and her instincts were proven correct when Carlos showed up on her doorstep with his mob associate Johnny Zacchara. Johnny required medical care but could not be seen at the hospital so Sabrina tended to his gunshot would. While Carlos and Johnny hid from the authorities in her home, Carlos admitted that he had shot Ava and as a result Ava was presumed deceased. Carlos insisted that Ava deserved payback for the threats she had made against Sabrina and her unborn child but Sabrina disagreed.

Although Sabrina lost her position at General Hospital, Michael Corinthos planned to hire Sabrina to work at the free clinic which he hoped to build. When plans for the clinic were stalled, he offered her a job as a nanny for his infant sister Avery. Sabrina was hesitant to accept the position since Avery was Ava Jerome's daughter, the same child that Sabrina had almost harmed. Much to the dismay of Ava's older daughter Kiki, Sabrina took the position as Avery's nanny.