Calcium ions (Ca) are indispensable and versatile metal ions that play a pivotal role in regulating cell metabolism, encompassing cell survival, proliferation, migration, and gene expression. Aberrant Ca levels are frequently linked to cell dysfunction and a variety of pathological conditions. Therefore, it is essential to maintain Ca homeostasis to coordinate body function. Disrupting the balance of Ca levels has emerged as a potential therapeutic strategy for various diseases, and there has been extensive research on integrating this approach into nanoplatforms. In this review, the current nanoplatforms that regulate Ca homeostasis for cancer therapy are first discussed, including both direct and indirect approaches to manage Ca overload or inhibit Ca signalling. Then, the applications of these nanoplatforms in targeting different cells to regulate their Ca homeostasis for achieving therapeutic effects in cancer treatment are systematically introduced, including tumour cells and immune cells. Finally, perspectives on the further development of nanoplatforms for regulating Ca homeostasis, identifying scientific limitations and future directions for exploitation are offered.