It is well known that biochemical changes in cancer cell occur in response to environmental cues and during migration. However, information about changes in the physical properties (e.g., volume, elasticity) of cancer cells during migration and/or in response to physical modulations (confinement and perturbations). We report the use of a near-infrared (NIR) laser microbeam system integrated with a NIR digital holographic microscopy (DHM) to study physical response of cancer cells. The cancer cells were cultured in microfluidic devices and subjected to different physical confinement (controlled by channel geometry), osmolarity changes of extracellular medium and/or laser-induced perturbations. The changes in optical thickness (or phase map) of the cells were monitored with high spatial and temporal resolution during and after the physico-chemical perturbations. A weakly-focused continuous-wave laser microbeam was used to impart radiation pressure on cell membrane and the changes in thickness were monitored using DHM to estimate elasticity. Further, an ultrafast tightly-focused laser microbeam was used to allow extracellular fluid flow into the cell or from the cytoplasm under different osmolarity conditions. Dynamic changes in physical properties of various cells and observed differences in responding to different physical/chemical environment/perturbations will be presented.