Climate change triggers increases in temperature, drought, and/or salinity that threaten potato production, because they necessitate specific amounts and quality of water, meanwhile lower temperatures generally support stable crop yields. Various cultivation techniques have been developed to reduce the negative effects of drought, heat and/or salinity stresses on potato. Developing innovative varieties with relevant tolerance to abiotic stress is absolutely necessary to guarantee competitive production under sub-optimal environments. Commercial varieties are sensitive to abiotic stresses, and substantial changes to their higher tolerance levels are not easily achieved because their genetic base is narrow. Nonetheless, there are several other possibilities for genetic enhancement using landraces and wild relatives. The complexity of polysomic genetics and heterozygosity in potato hamper the phenotype evaluation over abiotic stresses and consequent conventional introgression of tolerance traits, which are more challenging than previous successes shown over diseases and insects resistances. Today, potatoes face more challenges with severe abiotic stresses. Potato wild relatives can be explored further using innovative genomic, transcriptomic, proteomic, and metabolomic approaches. At the field level, appropriate cultivation techniques must be applied along with precision farming technology and tolerant varieties developed from various breeding techniques, in order to realize high yield under multiple stresses.