Abstract Background Molecular Tumor Boards (MTBs) are pivotal in the current management of oncological patients, integrating molecular diagnostics with clinical expertise to tailor precise treatments. Within the framework of EU-funded ‘Building EU Cancer and Public Health Genomics platform’ (Can.Heal) project that aims at streamlining genomics implementation in public health, we are developing a policy brief to promote MTBs’ adoption across the EU. Methods A two-step approach was employed to delineate strategies for MTB implementation. Firstly, we conducted a systematic review and meta-analyses (if feasible) up to November 2023, on studies assessing the MTBs’ clinical impact. Secondly, based on the results of the review, we conducted an expert consultation to identify key areas to improve MTBs implementation and impact. Results 48 studies were included, whose results were heterogeneous in terms of organizational aspects and number of experts involved (mean n: 6, range: 2-19). Average implementation rate of the recommendations issued by the MTB was 43.1% (3.2%-92%), with a turnaround time from testing to recommendation of 36 days (15-58). By pooling data from 12 studies (n = 1623), a favorable overall survival [HR = 0.63 (95% CI 0.53-0.76), I2 42.0%] was reported for patients managed in hospitals with MTBs versus not. Similar estimates were reported when the outcome was progression free survival [HR = 0.63 (95% CI 0.54-0.72), I2 = 0.0%], based on 8 studies (n = 1106). The subsequent expert consultation identified 5 key areas for MTB implementation: genetic data sharing, standards for results’ interpretation, equitable access to MTB, optimization of the testing process, and funding and reimbursement. Conclusions The policy brief underscores the significant clinical benefits of MTB-recommended therapy, improving patients’ outcomes. Nevertheless, addressing resource allocation and infrastructure development is essential to optimize MTB utilization and enhance patient outcomes. Key messages • Our results highlight that MTBs-recommended therapy translates into tangible clinical benefits. • More fundings and resources are needed to optimize and fully implement MTBs in clinical practice.