Problem: Complex systems are composed of many interdependent subsystems with a level of complexity that exceeds the ability of a single designer. One way to address this problem is to partition the complex design problem into smaller, more manageable design tasks that can be handled by multiple design teams. Partitioning-based design methods are decision support tools that provide mathematical foundations, and computational methods to create such design processes. Managing the interdependency among these subsystems is crucial and a successful design process should meet the requirements of the whole system which needs coordinating the solutions for all the partitions after all. Approach: Partitioning and coordination should be performed to break down the system into subproblems, solve them and put these solutions together to come up with the ultimate system design. These two tasks of partitioning-coordinating are computationally demanding. Most of the proposed approaches are either computationally very expensive or applicable to only a narrow class of problems. These approaches also use exact methods and eliminate the uncertainty. To manage the computational complexity and uncertainty, we approximate each subproblem after partitioning the whole system. In engineering design, one way to approximate the reality is using surrogate models (SM) to replace the functions which are computationally expensive to solve. This task also is added to the proposed computational framework. Also, to automate the whole process, creating a knowledge-based reusable template for each of these three steps is required. Therefore, in this dissertation, we first partition/decompose the complex system, then, we approximate the subproblem of each partition. Afterwards, we apply coordination methods to guide the solutions of the partitions toward the ultimate integrated system design. Validation: The partitioning-approximation-coordination design approach is validated using the validation square approach that consists of theoretical and empirical validation. Empirical validation of the design architecture is carried out using two industry-driven problems namely the a hot rod rolling problem’, ‘a dam network design problem’, ‘a crime prediction problem’ and ‘a green supply chain design problem’. Specific sub-problems are formulated within these problem domains to address various research questions identified in this dissertation. Contributions: The contributions from the dissertation are categorized into new knowledge in five research domains: • Creating an approach to building an ensemble of surrogate models when the data is limited – when the data is limited, replacing computationally expensive simulations with accurate, low-dimensional, and rapid surrogates is very important but non-trivial. Therefore, a cross-validation-based ensemble modeling approach is proposed. • Using temporal and spatial analysis to manage the uncertainties - when the data is time-based (for example, in meteorological data analysis) and when we are dealing with geographical data (for example, in geographical information systems data analysis), instead of feature-based data analysis time series analysis and spatial statistics are required, respectively. Therefore, when the simulations are for time and space-based data, surrogate models need to be time and space-based. In surrogate modeling, there is a gap in time and space-based models which we address in this dissertation. We created, applied and evaluated the effectiveness of these models for a dam network planning and a crime prediction problem. • Removing assumptions regarding the demand distributions in green supply chain networks – in the existent literature for supply chain network design, there are always assumptions about the distribution of the demand. We remove this assumption in the partition-approximate-compose of the green supply chain design problem. • Creating new knowledge by proposing a coordination approach for a partitioned and approximated network design. A green supply chain under online (pull economy) and in-person (push economy) shopping channels is designed to demonstrate the utility of the proposed approach.