The NIH policy on sex as biological variable (SABV) emphasized the importance of sex-based differences in precision oncology. Over 50% of clinically actionable oncology genes are sex-biased, indicating differences in drug efficacy. Research has identified sex differences in non-reproductive cancers, highlighting the need for comprehensive sex-based cancer data. We therefore developed OncoSexome, a multidimensional knowledge base describing sex-based differences in cancer (https://idrblab.org/OncoSexome/) across four key topics: antineoplastic drugs and responses (SDR), oncology-related biomarkers (SBM), risk factors (SRF) and microbial landscape (SML). SDR covers sex-based differences in 2051 anticancer drugs
SBM describes 12 551 sex-differential biomarkers
SRF illustrates 350 sex-dependent risk factors
SML demonstrates 1386 microbes with sex-differential abundances associated with cancer development. OncoSexome is unique in illuminating multifaceted influences of biological sex on cancer, providing both external and endogenous contributors to cancer development and describing sex-based differences for the broadest oncological classes. Given the increasing global research interest in sex-based differences, OncoSexome is expected to impact future precision oncology practices significantly.