Malignant psoas syndrome (MPS) was first described in 1990, and is characterized by proximal lumbosacral plexopathy, painful fixed flexion of the ipsilateral hip, and radiological or pathological evidence of ipsilateral psoas major muscle malignant involvement. There have been 23 case reports of MPS in medical journals. Despite being associated with a severe and difficult pain, there is no definitive approach to management presented in the palliative care literature. We review the relevant clinical features and the subsequent multidisciplinary pain management in relation to four new cases of malignant involvement of the psoas muscle, and the 23 case reports in the literature. We propose that MPS comprises a continuum of symptoms and signs related to the degree of anatomical destruction with associated inflammatory reaction and muscle spasm, and also the degree of lumbosacral plexopathy causing neuropathic pain. A protocol is presented for the management of the complex pain issues of MPS directed at likely mechanisms. The treatment options include opioids, agents for neuropathic pain, muscle relaxants to manage psoas muscle spasm, and anti-inflammatory agents to reduce peritumoral edema. Direct anti-tumor measures also need to be considered. Further prospective study is needed to validate the proposed methods of assessment and treatment.