This review focuses on the recent developments and optimization of magnetic nanoparticles (MNPs) containing Gd, Mn, Fe, and other lanthanide ions that can function as dual-mode T1–T2 MRI contrast agents (DMCAs). DMCAs induce positive or negative contrast in the same MRI scanner by changing its operational mode between T1-weighted and T2-weighted pulse sequences. The type of contrast they induce depends critically on their r2/r1 relaxivity ratio, which should be in the 2–10 range for optimal performance. The review begins with a brief discussion of the basic principles of paramagnetic relaxation in MNPs, followed by an overview of strategies for designing DMCAs, including the use of NPs with a single type of contrast material (e.g., Gd- or Mn-based NPs) or both types of contrast materials in the same nanoplatform. Examples of in vivo preclinical applications are provided, highlighting the advantages and disadvantages of each approach. The review also discusses the challenges and limitations of designing efficient DMCAs, emphasizing the importance of controlling the r2/r1 ratio to achieve optimal performance.This review focuses on the recent developments and optimization of magnetic nanoparticles (MNPs) containing Gd, Mn, Fe, and other lanthanide ions that can function as dual-mode T1–T2 MRI contrast agents (DMCAs). DMCAs induce positive or negative contrast in the same MRI scanner by changing its operational mode between T1-weighted and T2-weighted pulse sequences. The type of contrast they induce depends critically on their r2/r1 relaxivity ratio, which should be in the 2–10 range for optimal performance. The review begins with a brief discussion of the basic principles of paramagnetic relaxation in MNPs, followed by an overview of strategies for designing DMCAs, including the use of NPs with a single type of contrast material (e.g., Gd- or Mn-based NPs) or both types of contrast materials in the same nanoplatform. Examples of in vivo preclinical applications are provided, highlighting the advantages and disadvantages of each approach. The review also discusses the challenges and limitations of designing efficient DMCAs, emphasizing the importance of controlling the r2/r1 ratio to achieve optimal performance.