Cancer-associated thrombosis (CAT) is a devastating complication of cancer that can significantly impact a patient’s health and life. The incidence of CAT is approximately 20%, and 1 in 5 cancer patients will develop CAT annually. Indeed, CAT can promote pulmonary embolism and deep vein thrombosis, leading to increased morbidity and mortality that dramatically impact survival. CAT can also provoke delay or discontinuation of anticancer treatment, which may result in a lack of treatment efficacy and high costs for patients, institutions, and society. Current guidelines advocate direct oral anticoagulants (DOACs) as the first-line anticoagulant option in CAT. Compared to low-molecular-weight-heparins (LMWHs), DOACs are advantageous in that they typically have an oral route of administration, do not require laboratory monitoring, and have a more predictable anticoagulant effect. However, in patients with thrombocytopenia, renal failure, or those receiving anticancer regimens with potential for drug-drug interactions, LMWH is still the mainstay of care. The main limitation of current anticoagulant agents is related to bleeding risk (BR), both for DOACs and LMWHs. Specifically, DOACs have been associated with high BR in gastrointestinal and genitourinary cancers. In this challenging scenario, abelacimab, an anti-factor XI agent, could represent a viable option in the management of CAT due to its “hemostasis sparing” effect. The safe profile of abelacimab could be useful in patients with active malignancy and CAT, as long-term anticoagulant therapy is often required. Two ongoing international phase III trials (Aster and Magnolia) compare abelacimab with the standard of care (i.e., apixaban in patients with CAT and dalteparin in those with CAT and high BR, respectively). Abelacimab is a new and attractive anticoagulant for the management of CAT, especially in the insidious and critical scenario of active cancer patients with venous thromboembolism and high BR. The aim of this narrative review is to discuss the updated evidence on the performance of DOACs and LMWHs in the treatment of CAT and to focus on the potential role of abelacimab in CAT and its promising associated clinical trials.