Set against the backdrop of Pittsburgh in 1996, crafts the narrative of Jamie, portrayed by the charismatic Jake Gyllenhaal, as he navigates the tumultuous waters of post-failure life. Initially employed at an electronics store, Jamie's undeniable charm and flirtatious demeanor lead him to more than just satisfied customers; however, it also results in his eventual dismissal after an intimate encounter with Christy, the girlfriend of his employer, is publicly broadcast for everyone, including her boyfriend, to hear.

Jobless, Jamie finds himself at his familial dinner table, where the stark contrast between his achievements and those of his successful family members is glaring. Surrounded by his doctor father and sister, and his affluent brother Josh, wealthy from his medical software enterprise, Jamie hints at a fresh start through Josh’s help in securing a position as a pharmaceutical sales representative. This marks the initiation of his association with Pfizer, following his participation in several training sessions.

However, Jamie's foray into the world of pharmaceutical sales proves challenging. Attempting to sell Zoloft and Zithromax, he meets consistent resistance from doctors, much to the lament of his partner Bruce, who envisions Jamie as his ticket out to the grandeur of the big leagues in Chicago, where his family awaits. Bruce hatches a plan for Jamie to sway Dr. Knight from prescribing Prozac to Zoloft, insinuating that his influence would domino into broader acceptance across the medical community. Reveling in his quick wit, Jamie exploits his charm with receptionists and resorts to crafty maneuvers like discarding Dr. Knight's Prozac samples, alongside offering bribes, to earn favor.

During a shambolic scheme, Jamie, posing as an intern, encounters Maggie—captivatingly played by Anne Hathaway—who is grappling with early-onset Parkinson’s Disease. This budding dynamic takes an unorthodox turn following their initial meeting, marked by a slap delivered by Maggie in retaliation to Jamie's charade and audacity. Intrigued rather than deterred, Jamie pursues Maggie, initiating a relationship anchored in casual encounters that soon burgeons into emotional complexity.

Parallel to his escalating relationship with Maggie, Jamie’s professional narrative shifts dramatically with the introduction of Viagra, marking a turning point that amplifies his popularity among doctors. Yet, despite professional contentment, his personal entanglement with Maggie extends into deeper realms as he discovers the constraints her illness imposes. Maggie’s nurse-job, sans health insurance, propels Jamie further into advocating for a deeper relationship—a notion initially rebutted by Maggie due to her reluctance to entangle him in her medical plight.

Through a serendipitous attendance at a Parkinson’s convention suggested by a fellow attendee who notices her tremors, Maggie confronts the broader discourse surrounding her condition, deeply moved by narratives shared by those present. Jamie, conversely, faces apprehension fueled by a conversation with a once-hopeful husband resigned to his wife’s terminal stage of the disease. Despite internal trepidations, Jamie attempts to remain steadfast, driven by Maggie’s rekindled hope. However, their relationship stumbles on the rocky path of desperation as Jamie exhaustively seeks cures and solutions, only for Maggie to resign to the futility of it, resulting in their separation.

Jamie’s glum loneliness finds him momentarily immersed in empty hedonism, punctuated by a night of excess leading to a revealing conversation with his brother Josh, who opts to rekindle his marriage, inadvertently reflecting Jamie’s own unfulfilled longing. Meanwhile, a chance reunion with Maggie prompts an introspective journey, as evidenced by a heartfelt self-made video they shared, leading to the epiphany that her companionship, despite its challenges, is worth the emotional investment.

In a dynamic climax reminiscent of the fervent resolve seen in romantic comedies, Jamie engages in a desperate pursuit, halting a Canada-bound bus to implore Maggie once more. His earnest confession reflects profound growth, acknowledging the trials of health challenges while cherishing the integrity of their shared reality over any other possible scenario. His impassioned declaration encapsulates an acceptance and willingness to embrace her complexities, not out of obligation but genuine affection.

The closing montage serves as a poignant reminder of life’s transient nature, advocating for living each day with purpose while juxtaposing Jamie’s renewed ambition. United with Maggie, the narrative concludes on a hopeful note of Jamie returning to medical studies, embracing an uncertain yet undeterred future inspired by love and personal evolution. In essence, deftly juxtaposes the alluring transience of professional success against the enduring complexities of human emotions, ultimately finding its zenith in the embrace of life’s intrinsic unpredictability while idolizing love's redemptive potential.