Cancer patients are at increased risk for venous thromboembolism (VTE), which further increases with advanced stages of malignancy, prolonged immobilization, or prior history of thrombosis. To reduce VTE-related mortality, many official guidelines encourage the use of thromboprophylaxis (TPX) in cancer patients in certain situations, e.g., during chemotherapy or in the perioperative period. TPX in the end-of-life care, however, remains controversial. Most recommendations on VTE prophylaxis in cancer patients are based on the outcomes of clinical trials that excluded patients under palliative or hospice care. This translates to the paucity of official guidelines on TPX dedicated to this group of patients. The problem should not be underestimated as VTE is known to be associated with symptoms adversely impacting the quality of life (QoL), i.e., limb or chest pain, dyspnea, hemoptysis. In end-of-life care, where the assurance of the best possible QoL should be the highest priority, VTE prophylaxis may eliminate the symptom burden related to thrombosis. However, large randomized studies determining the benefits and risks profiles of TPX in patients nearing the end of life are lacking. This review summarized available data on TPX in this population, analyzed potential tools for VTE risk prediction in the view of this group of patients, and summarized the most current recommendations on TPX pertaining to terminal care.