Miniaturization of biological and chemical assays in lab-on-a-chip systems is a highly topical field of research. The pressure-driven droplet-based microfluidic platform is a promising way to realize these miniaturized systems by expanding the capability of assays with special features that are unreached by traditional workflows. Full custom centric design of droplet-based microfluidic lab-on-a-chip systems leads to a high system integration level and design complexity. Therefore advanced development automation methodologies are required, comparable with the methods and tools which are off-the-shelf technology in electronic design automation. Our design and simulation toolkit meets these requirements for a versatile and low-risk development of custom lab-on-a-chip devices. We used the system simulation approach for the fast and precise simulation of complex microfluidic networks. Together with our conceptual model of microfluidic networks, the simulation algorithm solves the development problems arising with complex lab-on-a-chip applications. We confirmed these by reference and benchmark experiments. The results show the correct reproduction of experimental measurements by the simulation. The algorithm enables efficient application-driven development of lab-on-a-chip devices. As a result, the advantages of lab-on-a-chip will be accessible for more people through the easy, versatile and efficient transformation from complex laboratory workflows to compact and easy to use lab-on-a-chip applications.