An analytical methodology is presented for the systematic design of a serial kinematic flexure-guided high speed nanopositioning scanner. Approximate relations for the first natural frequency in different directions, achievable range, and in-plane cross-coupling between the axes are obtained considering each stage as a simple one-dimensional mass spring system. Parametric studies are performed to compare these characteristics for a particular range of flexure dimensions. The robustness of the design to manufacturing tolerances, and especially their influence on cross-coupling is investigated. The relations obtained are experimentally verified on a single-axis test system and the measured natural frequencies closely match analytical and FEA predictions. A two-axis nanopositioning system is designed, which has the fast and slow scanning axes’ resonances at 26.36 kHz and 5.28 kHz. The design is validated using finite elements, and the predicted actuation-direction resonances (25.5 kHz and 5.24 kHz respectively) closely agree with those found analytically.