A region within a body of an imaging subject can be imaged to identify a tumor locus in a three dimensional coordinate system. An opening in the body of the imaging subject can be formed to provide an access location. Using an actuator, a surgical tool can be guided to traverse the access location to access the tumor locus, the surgical tool guided along a specified trajectory in the three dimensional coordinate system by the actuator and configured to resect and remove a first portion of the tumor within the tumor locus.