This paper presents a nanomanipulation system for operation inside scanning electron microscopes (SEM). The system is small in size, capable of being mounted onto and demounted from an SEM through the specimen exchange chamber without breaking the high vacuum of the SEM. This advance eliminates frequent opening of the high-vacuum chamber, thus, incurs less contamination to the SEM, avoids lengthy pumping, and significantly eases the exchange of end-effectors (e.g., nano probes and grippers). The system consists of two independent 3-DOF Cartesian nanomanipulators based on piezo motors and piezo actuators. High-resolution optical encoders are integrated into the nanomanipulators to provide position feedback for closed-loop control. A look-then-move control system and a contact detection algorithm are implemented for horizontal and vertical nanopositioning. The system design, system characterization details, and system performance are described.