Therefore, in this review, we focus on the key mechanisms involved in resistance to chemotherapy in osteosarcoma CSCs, namely, detoxification systems (drug efflux transport and ALDH), survival-related pathways (ERK, AKT), adaptive metabolic routes, altered cell cycle and DNA repair, enhanced apoptosis and modulation of the tumor microenvironment (hypoxia, inflammation), by giving appropriate examples. Here, LDHA is linked to neoplasm.