Research work over the past decade has emphasized the importance of reliability and maintenance in chemical process operation and the benefits from maintaining process availability levels that optimize the trade-offs between maintenance costs and plant profitability. On the other hand, traditional reliability and maintenance methodologies focus on keeping the process functioning without distinguishing between different performance levels. In this work a system effectiveness measure is introduced depending on the design and operation as well as the reliability and maintainability characteristics of the process, capturing their impact upon process performance. Furthermore, a rigorous mathematical framework is proposed with which these interactions can be quantified and, therefore, the optimal process design operation and maintenance policy can be identified. This is depicted by implementing the proposed approach on a process example.