The advantages of combined simulation techniques have been already frequently discussed and are well-covered by the recently published literature. In particular, many case studies have been presented solving similar domain-specific problems by different multi-paradigm simulation approaches. Moreover, a number of papers exist focusing on theoretical and conceptual aspects of hybrid simulation. However, it still remains a challenge to decide, whether combined methods are appropriate in certain situations and how they can be applied. Therefore, domain-specific user guides for multi-paradigm modeling are required combining general concepts and best practices to common steps. In this paper, we particularly outline three major processes targeting to define structured hybrid approaches in domain-specific contexts, and we focus on some practical issues aiming to a sustainable model development. Finally, an example hybrid methodology for problems in healthcare will be presented.