Nano‐CaO2, with its multifunctional properties, has emerged as a promising candidate for tumor therapy. Its ability to release Ca2+ and H2O2 into the tumor microenvironment has positively modulated abnormal calcium signaling and kinetic therapy. Moreover, the indirectly produced O22− by CaO2 can alleviate hypoxic conditions. On the one hand, the accumulation of Ca2+ can lead to various tumor cell apoptosis events, such as calcium overload and tumor calcification. On the other hand, the released H2O2 can convert into more toxic reactive oxygen species (ROS) via exogenous stimulation and endogenous regulation, thereby making nano‐CaO2 a versatile tool in modern medicine, exhibiting its invaluable and irreplaceable medical value in tumor therapy. Hence, a comprehensive review of the recent advances in the nano‐CaO2 platform is imperative. This review provides an overview of the conventional synthesis strategies for nano‐CaO2. It elucidates the potential role of the nano‐CaO2 nanoplatforms in various tumor treatment strategies, including monotherapy and combination therapy, in detail. Given the remarkable outcomes achieved to date and the challenges that of future clinical translation, this work predicts the future research directions. This review will encourage further development of the metal oxide nanomedicine family, epitomized by nano‐CaO2.