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This paper proposes an agile model-based systems engineering (SE) methodology (LITHE methodology) to engineer the contemporary large, complex, and interdisciplinary systems of systems. The methodology relates the processes, the methods, and the tools in order to support an effective model-based development context. The LITHE uses a universal and intuitive SE base process, reducing the complexity and intricacy of the base methods, emphasizing the agile principles such as continuous communication, feedback and stakeholders' involvement, short iterations, and rapid response, and rousing the utilization of a coherent system model developed through the benchmark systems graphical modeling languages. Aiming to support the development of successful systems, which satisfy the stakeholders' expectations, the methodology is particularly concerned with human systems integration, so the related fundamental aspects are considered throughout the engineering process. The LITHE methodology also includes a supporting graphical tool that aims to be an agile instrument to be used by systems engineers in a model-based development environment. To illustrate the effectiveness of the proposed methodology and to provide some validation, an empirical case study related with the development of a real large and complex system (the Guiding Urban Intelligent Traffic and Environment system) is also described.