Patients with central nervous system (CNS) metastases have a poor prognosis, which is generally worse than in those with disease only outside the CNS. Treatment options for CNS metastases are still limited and suboptimal. New systemic therapies such as targeted therapies and immunotherapy have emerged for different cancers and differences in survival of patients with CNS metastases by tumour subtype have been observed. A better knowledge on the evolving epidemiology and biology of CNS metastases are key elements in the development of new treatment strategies whereby the identification of promising therapeutic targets for new compounds may play an important role in improving patient outcome. This article will provide a general overview of the recent improvement in systemic therapies for CNS metastases, highlighting perspectives to improve the management of CNS metastases and introduce the BrainStorm program- an innovative research program from the Oncodistinct network aiming to overcome the challenges of CNS metastases.