Cadmium (Cd) contamination poses a threat to global crop safety. To address this issue, researchers mainly focused on the Cd, explored mechanism of accumulation to low-Cd breeding technologies and created several low-Cd varieties over the past decades. However, new challenges have emerged, particularly the yield reduction due to disturbances in mineral nutrient balance. The goals of breeding have been transferred from a primary focus on ‘low-Cd crops’ to ‘low-Cd/nutrient-balanced’ crops, which means limiting Cd content while maintaining other nutrient elements like iron (Fe), manganese (Mn) and zinc (Zn) at a proper content, thus to meet the future agricultural demands. Here, on a multielement perspective, we reviewed the mechanisms of Cd and mineral nutrient transport system in crops and summarized the research advances in Cd minimization through artificial mutations, natural variations and genetic engineering. Furthermore, the challenge of disruption of mineral nutrients in low-Cd crops was discussed and two potential approaches designing Cd-mineral nutrient-optimized artificial transporters and pyramiding Cd-mineral nutrient-optimized variations were proposed. Aiming at addressing these challenges, these approaches represent promising advancements in the field and offer potential pathways for future research and development in the creation of safe and high-quality crops.