Most state-of-the-art multibody systems are multidisciplinary and encompass a wide range of components from various domains such as electrical, mechanical, hydraulic, pneumatic, etc. The design considerations and design parameters of the system can come from any of these domains or from a combination of these domains. In order to perform analytical design sensitivity analysis on a multidisciplinary system (MDS), we first need a uniform modeling approach for this class of systems to obtain a unified mathematical model of the system. Based on this model, we can derive a unified formulation for design sensitivity analysis. In this paper, we present a modeling and design sensitivity formulation for MDS that has been successfully implemented in the MIXEDMODELS (Multidisciplinary Integrated eXtensible Engine for Driving Metamodeling, Optimization and DEsign of Large-scale Systems) platform. MIXEDMODELS is a unified analysis and design tool for MDS that is based on a procedural, symbolic-numeric architecture. This architecture allows any engineer to add components in his/her domain of expertise to the platform in a modular fashion. The symbolic engine in the MIXEDMODELS platform synthesizes the system governing equations as a unified set of non-linear differential-algebraic equations (DAE’s). These equations can then be differentiated with respect to design to obtain an additional set of DAE’s in the sensitivity coefficients of the system state variables with respect to the system’s design variables. This combined set of DAE’s can be solved numerically to obtain the solution for the state variables and state sensitivity coefficients of the system. Finally, knowing the system performance functions, we can calculate the design sensitivity coefficients of these performance functions by using the values of the state variables and state sensitivity coefficients obtained from the DAE’s. In this work we use the direct differentiation approach for sensitivity analysis, as opposed to the adjoint variable approach, for ease in error control and software implementation. The capabilities and performance of the proposed design sensitivity analysis formulation are demonstrated through a numerical example consisting of an AC rectified DC power supply driving a slider crank mechanism. In this case, the performance functions and design variables come from both electrical and mechanical domains. The results obtained were verified by perturbation analysis, and the method was shown to be very accurate and computationally viable.