Cancer-related stroke (CRS), referring to ischemic stroke occurring in cancer patients without other clear etiology, represents a clinical challenge, as it is associated with unfavorable clinical outcomes including high rates of recurrence and mortality. There are scarce international recommendations and limited consensus statements on CRS management. For this comprehensive overview, the available studies/reviews/meta-analyses on the use of acute reperfusion and secondary prevention treatments for cancer patients with ischemic stroke, focusing on antithrombotic agents, were collected and summarized. A practical management algorithm was designed per the available data. In short, acute reperfusion in the form of intravenous thrombolysis and mechanical thrombectomy appears to be safe in CRS and can be considered for eligible patients, though the functional outcomes are often poor, and mostly defined by the preexisting condition. Many patients carry indications for anticoagulation, in which case vitamin K antagonists are not preferred, while low-molecular weight heparins remain the treatment of choice; direct oral anticoagulants can be alternatively considered but are contraindicated for gastrointestinal malignancies. For patients without clear anticoagulation indications, no net benefit for anticoagulation compared to aspirin has been shown. Other targeted treatment options should be evaluated in an individualized approach, alongside the appropriate management of conventional cerebrovascular risk factors. Oncological treatment should be swiftly initiated/continued. In conclusion, acute CRS remains a clinical challenge, with many patients suffering recurrent stroke, despite preventive measures. More randomized-controlled clinical trials are urgently needed to pinpoint the most effective management options for this subset of stroke patients.