Low back pain is a common secondary health condition after lower limb amputation with important implications related to functional capabilities and overall quality of life. Despite the high prevalence of low back pain after lower limb amputation, the underlying etiologies of the disorder remain unknown. This hypothesis-driven communication provides evidence in support of using the multifactorial, biopsychosocial model of low back pain experience in the general population for identification of potential risk factors and rehabilitation targets for low back pain after lower limb amputation. Key findings that link biological, psychological, and social factors and the experience of low back pain in the general patient population with LBP are discussed while highlighting gaps in our current state of knowledge related to the association of these factor and presence of low back pain after lower limb amputation. Importantly, the aim of this communication was not to propose a new model, but rather to organize data originating from prior work into a coherent hypothesis-driven conceptual framework to better understand the need for multifaceted and multidisciplinary intervention approaches for effective treatment of low back pain after lower limb amputation.