The burden of morbidity and mortality from SARS-CoV-2 infection is especially significant in heart transplant patients who are at higher risk for poor outcomes owing to immunosuppression, blunted response to vaccination, and multiple comorbid conditions. Over the last 3 years the therapeutic landscape for COVID-19 has evolved and our drug armamentaria continues to expand. With these advancements comes a time of great hope to mitigate significant illness from SARS - CoV - 2 infection. However, as with many emerging frontiers, the administration of novel therapeutics to a complex patient population remains challenging. We present a patient case encountered at our institution that highlights the need for increased awareness of nuances while managing COVID-19 infection in a heart transplant recipient.