Multiple myeloma (MM) is the second most common hematologic malignancy with high morbidity and mortality indices. The emerging risk factors and complex pathogenic mechanisms surrounding the disease evolution are challenging. Thus, understanding these risk factors and the pathogenic basis of the disease will lead to better interventions and targeted therapies. We conducted an integrated review of the literature on MM, risk assessment, pathogenic mechanisms, and the evolution of anti-myeloma target therapies using PubMed, Medline, CINAHL, Google Scholar, African Journal Online, and Cochrane databases. The review analyzed the prevalence, risk factors, and pathogenesis of MM, as well as highlights antimyeloma therapies. The literature indicates that eight risk factors are linked with MM, and two major pathogenic pathways are paramount in its evolution. We identified nine antimyeloma targeted pathways including immunomodulatory agents, proteasome inhibitors, monoclonal antibodies, fibrin growth factor receptor inhibitors, histone deacetylase inhibitors, BCL inhibitors, immune checkpoint inhibitors, chimeric antigen receptor T-cell and B-cell maturation antigen-targeted monoclonal antibody. To holistically address the burden of MM, there is need for in-depth knowledge of the environmental risk factors and disease pathogenic mechanisms. The cytogenetic, immunologic, and skeletal mechanisms that lead to disease evolution play significant roles in risk stratification, prognostication, and emergence of new antimyeloma therapies. A policy on MM risk assessment is therefore strongly recommended for exposed target population.