Introduction: Targeted muscle reinnervation (TMR) is increasingly common in the care of major limb amputation to limit amputation-related pain. This review aims to elucidate how chronic pain states and length of delay prior to TMR affect its success and outcomes. Methods: Manuscripts were collected from three databases. Articles were first screened and excluded based on exclusion criteria. The remaining manuscripts were independently reviewed to determine inclusion. Article and patient demographics, as well as pain outcomes, were extracted. Data were analyzed based on pain condition, amputation vs. neuroma, and time from amputation/injury to surgery. Results: The literature search yielded 723 articles, with 41 meeting the inclusion criteria. Twenty-one articles included patients with residual limb pain (RLP) and phantom limb pain (PLP), including 14 on amputation and 6 on neuroma excision. Five articles included cancer-related amputation. Complex Regional Pain Syndrome (CRPS) was discussed in 3 articles, ischemia or infection in 2 articles, and neurofibromatosis 1 in 1 article. Twenty-two articles described TMR at the time of amputation. Conclusions: TMR is effective at preventing neuroma formation and limiting pain when performed at the time of amputation. Delayed patients had a greater improvement in RLP but less of an improvement in PLP, when assessed against immediate TMR patients who were compared to non-TMR standard amputees. In the presence of chronic pain states, such as CRPS, there is also improved analgesia. However, current clinical data are limited, indicating a need for further research into the use of TMR for chronic pain management.