Closed cavity adjustable sensor mount systems include a sealed, closed cavity enclosing a sensor and forming a closed cavity sensor assembly. The closed cavity sensor assembly may be tilted and/or translated relative to a platform in order to adjust the orientation of the sensor to align it with an imaging optical axis. Following alignment, the closed cavity sensor assembly may be permanently or reversibly fixed in place. The closed cavity adjustable sensor mount systems may be part of medical imaging systems such as endoscopic imaging systems and/or open field imaging systems.