Advanced age is one of the major determinants of frailty in patients with cancer-associated thrombosis. However, multiple other factors contribute to frailty in these patients. The identification of frailty in patients with cancer-associated thrombosis is critical as it influences the complexity of the anticoagulant treatment in this population at high risk of venous thromboembolism and bleeding. Factors that contribute to frailty in patients with cancer-associated thrombosis include age, type of cancer, comorbidities such as chronic kidney disease, poly-pharmacotherapy, treatment compliance, cognitive impairment, anemia, thrombocytopenia, mobility, nutritional status, Eastern Cooperative Oncology Group grade, risk of falls, and reduced life expectancy. In the absence of specific clinical studies current anticoagulant treatment guidelines for the management are not fully applicable to frail patients with cancer. The anticoagulant treatment should therefore benefit from a tailored approach based on an algorithm that takes into account the specificities of the malignant disease.