Lately, there has been a great deal of emphasis on developing novel biomaterials for next generation biomedical technologies. Especially, research efforts have focused on biomaterials that meet the demand for precisely engineered three-dimensional structures. These research efforts seek to design advanced biomaterials that mimic the natural environments of tissues more closely, and thus enhance the functional performance of these materials. To this end, surface modification/functionalization of biomaterials is considered pivotal to achieve the goals. Recent progress in biomaterials fabrication techniques has shown huge promise for surface engineering of biomaterials leading to realization of devices that have complex surface geometries for various biomedical applications in the pharmaceutical and medical fields. These include next generation drug delivery, diagnosis and biosensors, to name a few. In this review, we have highlighted important surface modification processes that have been employed for surface engineering of biomaterials. Further, an overview of the cellular response of surface modified biomaterial is presented. We have also discussed precise engineering of three-dimensional surface modification of biomaterials by initiated chemical vapor deposition (i-CVD) method. Notable biomedical applications have been described. Finally, we have presented a brief future perspective.