Mitochondria are key players in regulating cellular metabolism. Short noncoding RNAs, or microRNAs (miRNAs), have become significant modulators of gene expression and cellular functions. Recent research has demonstrated the presence and activity of mitochondrial miRNAs (MitomiRs) in various cell types, including blood cells. The role of MitomiRNAs in metabolic reprogramming throughout blood cell formation, including their biosynthesis, function, and possible therapeutic implications, was discussed in this chapter. The discovery of mitochondrial microRNAs (MitomiRs) transformed our understanding of gene regulation in these critical organelles. These MitomiRs were discovered as they were influencing mitochondrial gene expression, with considerable effects on various cellular functions like oxidative stress responses, production of energy, and apoptosis during blood cell development.