Severe Acute Respiratory Distress Syndrome Coronavirus 2 (SARS CoV-2) and its new variant Omicron was propelling the surge in Coronavirus Disease (COVID-19) in India and the world over. COVID-19 is associated with various extrapulmonary manifestations leading to acute coronary syndrome (ACS) in many patients. In our case report, a 55-year-old male with carcinoma soft palate on neo-adjuvant chemotherapy and radiotherapy came to our hospital emergency in an unconscious state. Cardiopulmonary resuscitation was initiated in the emergency suite, he was revived and shifted to the critical care unit for post cardiac arrest management. Patient was hemodynamically unstable and started on vasopressor support, electrocardiogram showed ischemic changes in anterolateral leads with cardiac enzyme troponin-T was positive. A diagnosis of ACS was made and managed appropriately. The patient got stabilized over a few hours, reverse transcriptase-polymerase chain reaction (RT-PCR) test was positive for novel COVID-19. Since our institute is a L2 setting hospital with limited resources, he was shifted to a higher centre for effective COVID-19 management. ACS is a deadly manifestation in COVID-19 patients. Cancer patients are immuno-compromised with a propensity for the hypercoagulable state due to the disease itself. We suggest that Omicron a new variant of concern leading to COVID-19 with cancer burden can aggravate extrapulmonary manifestation in a vulnerable population. We should be extra careful in the management of these patients.