Abstract-There is a growing interest on exploiting interference (rather than avoiding it) to increase network throughput. In particular, the so-called successive interference cancellation (SIC) scheme appears very promising, due to its ability to enable concurrent receptions from multiple transmitters and interference rejection. Although SIC has been extensively studied as a physical layer technology, its research and advances in the context of multi-hop wireless network remain limited. In this paper, we try to answer the following fundamental questions. (i) What are the limitations of SIC? How to overcome such limitations? (ii) How to optimize the interaction between SIC and interference avoidance? How to incorporate multiple layers (physical, link, and network) in an optimization framework? We find that SIC alone is not adequate to handle interference in a multi-hop wireless network, and advocate the use of joint SIC and interference avoidance. To optimize the joint scheme, we propose a cross-layer optimization framework that incorporates variables at physical, link, and network layers. We use numerical results to affirm the validity of our optimization framework and give insights on how SIC and interference avoidance can complement each other in an optimal manner.