A multi-target positioning system based on a digital elevation model is proposed to realize the accurate positioning of multiple targets using the on-board optoelectronic equipment of an UAV. A multi-target positioning model based on the target vector is developed. The pixel coordinates of each target in the field of view are obtained through target detection. The boresight vector of each target can be obtained. The measurement data of each sensor in the drone and optoelectronic reconnaissance platform are combined to calculate the geographical position information of each target. For a flight height of 3000 m, the experimental results show that the positioning error for the main target is approximately 16 m, whereas that for the secondary target is approximately 26 m. The effect of the improved filtering model is analyzed. After filtering, the positioning error of the main target is reduced to 7 m, whereas that of the secondary target is reduced to approximately 11 m. The verification of the flight experiment demonstrates that the engineering effect is basically consistent with the simulation experiment result. This method has the advantages of good real-time positioning, a small error, and facile engineering application.