Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy in men and is frequently underdiagnosed. Sexual dysfunction, including erectile dysfunction (ED), decreased libido, and delayed ejaculation, may arise from androgen deficiency, but vascular and psychosocial factors often coexist. In primary care (PC), understanding and coordinating these dimensions is crucial.We present the case of a 46-year-old male with KS followed in PC since 2003. Clinical information was collected from endocrinology, urology, and vascular surgery. The patient was diagnosed with primary hypogonadism after bilateral testicular surgery for epidermoid cysts, with histology showing a Sertoli-cell-only pattern; cytogenetics later confirmed 47,XXY. Intramuscular testosterone was initiated, with adequate libido but persistent ED, delayed ejaculation, and performance anxiety. He developed obesity, dyslipidemia, and peripheral arterial disease. Trials of PDE-5 inhibitors gave inconsistent benefit, and psychogenic factors contributed. Management considerations included cardiovascular risk optimization, alternative testosterone formulations, lifestyle changes, and psychosexual counseling. Strengths include long-term multidisciplinary follow-up; limitations include lack of standardized outcomes and variable adherence.Although sexual dysfunction is recognized in KS, reports seldom detail the interplay of mechanisms in PC. This case shows that ED in KS extends beyond hypogonadism and highlights PC’s role as the coordinator for multidisciplinary and psychosocial care.Routine assessment of sexual function in KS is essential, as persistent ED often reflects multifactorial causes. PC can integrate hormonal, cardiovascular, lifestyle, and mental health interventions. Future practice should include early vascular screening, individualized testosterone delivery, and structured psychosexual support, while avoiding assumptions that all symptoms stem from KS.ED in KS is a multidimensional condition requiring coordinated care. PC clinicians are well positioned to synthesize specialist input, manage comorbidities, and address psychosocial contributors, improving diagnostic accuracy, outcomes, and long-term well-being.ED in KS is rarely attributable to a single mechanism. A holistic, interdisciplinary PC approach can optimize sexual function, quality of life, and long-term health. This case reinforces the importance of systematic evaluation of sexual dysfunction in KS.