Combinatorial therapies have been recently proposed to improve the efficacy of anti-cancer treatment.The SynergyFinder R package is a software used to analyze pre-clinical drug combination datasets.Here,we report the major updates to the SynergyFinder R package for improved interpretation and annotation of drug combination screening results.Unlike the exist-ing implementations,the updated SynergyFinder R package includes five main innovations.1)We extend the mathematical models to higher-order drug combination data analysis and implement dimension reduction techniques for visualizing the synergy landscape.2)We provide a statistical analysis of drug combination synergy and sensitivity with confidence intervals and P values.3)We incorporate a synergy barometer to harmonize multiple synergy scoring methods to provide a consensus metric for synergy.4)We evaluate drug combination synergy and sensitivity to pro-vide an unbiased interpretation of the clinical potential.5)We enable fast annotation of drugs and cell lines,including their chemical and target information.These annotations will improve the interpretation of the mechanisms of action of drug combinations.To facilitate the use of the R package within the drug discovery community,we also provide a web server at www.s ynergyfinderplus.org as a user-friendly interface to enable a more flexible and versatile analysis of drug combination data.