Tumor cell mechanobiology elucidates the biophysical mechanisms underlying metastasis, drug resistance and immune evasion by dissecting the mechanical properties of tumor cells and their microenvironment. In 2025, the deep integration of atomic force microscopy, microfluidics and mechanophenotyping chips enabled high-throughput and automated mechanical profiling of tumor cells, circulating tumor cells and tumor-derived extracellular vesicles from the nanoscale to the single-cell level, laying a technological foundation for liquid biopsy and mechanics-based classification. Nuclear mechanical switches during confined migration, remodeling of focal adhesions and the cytoskeleton, and mechanosensitive ion channels such as Piezo1 and TRPV4 have been systematically characterized, establishing a multistep mechanotransduction network from the plasma membrane to the nucleus. Discoveries involving matrix stiffening, contractility-driven nuclear drug efflux have tightly linked matrix stiffness and cellular contractility to clinical outcomes such as chemoresistance and tumor immunity. This review summarizes representative advances in 2025 in tumor cell mechanobiology from three perspectives: tumor cell mechanical measurement technologies, mechanotransduction mechanisms and mechanical remodeling of the tumor microenvironment.