In order to increase a nonlinear system’s state estimate precision, an iterated orthogonal simplex cubature Kalman filter (IOSCKF) is presented in this study for target tracking. The Gaussian-weighted integral is decomposed into a spherical integral and a radial integral, which are approximated using the spherical simplex-radial rule and second-order Gauss–Laguerre quadrature rule, respectively, and result in the novel simplex cubature rule. To decrease the high-order error terms, cubature points with appropriate weights are taken from the cubature rule and processed using the provided orthogonal matrix. The structure supporting the nonlinear Kalman filter incorporates the altered points and weights and the calculation steps; from this, the updated time and measurement can be inferred. The Gauss–Newton iteration is employed repeatedly to adjust the measurement update until the termination condition is met and the IOSCKF is attained. The proposed algorithms are applied in target tracking, including CV target tracking and spacecraft orbit tracking, and the simulation results reveal that the IOSCKF can achieve higher accuracy compared to the CKF, SCKF, and OSCKF. In spacecraft orbit tracking simulation, compared with the SCKF, the position tracking accuracy and velocity tracking accuracy of the OSCKF are increased by 2.21% and 1.94%, respectively, which indicates that the orthogonal transformation can improve the tracking accuracy. Furthermore, compared with the OSCKF, the position tracking accuracy and velocity tracking accuracy of the IOSCKF are increased by 2.71% and 2.97%, respectively, which indicates that the tracking accuracy can be effectively improved by introducing iterative calculation into the measurement equation, thus verifying the effectiveness of the method presented in this paper.