Monocytes and macrophages are crucial components of the innate immune system, playing diverse roles in homeostasis, immunity, and pathophysiology. These mononuclear phagocytes originate from bone marrow and can differentiate into tissue-resident macrophages (TRMs) or inflammatory macrophages in response to various stimuli. The recruitment and polarization of monocytes and macrophages into distinct phenotypes, such as M1 (pro-inflammatory) and M2 (anti-inflammatory), are regulated by chemokines, integrins, and other signaling molecules. Inflammatory conditions can lead to the activation of inflammasomes, which promote cytokine production and pyroptosis. Transcription factors and microRNAs (miRNAs) play essential roles in the polarization of macrophages, with miRNAs regulating gene expression at the post-transcriptional level. Metabolic reprogramming, including changes in glycolysis, fatty acid synthesis, and the tricarboxylic acid (TCA) cycle, is also involved in modulating macrophage function. Therapeutic interventions targeting monocytes and macrophages, such as blocking MIF, NLRP3, and integrins, show promise in treating inflammatory diseases. The plasticity and multifaceted roles of monocytes and macrophages make them attractive therapeutic targets, but developing effective strategies remains a challenge due to the complexity of their functions and the need for precise regulation.Monocytes and macrophages are crucial components of the innate immune system, playing diverse roles in homeostasis, immunity, and pathophysiology. These mononuclear phagocytes originate from bone marrow and can differentiate into tissue-resident macrophages (TRMs) or inflammatory macrophages in response to various stimuli. The recruitment and polarization of monocytes and macrophages into distinct phenotypes, such as M1 (pro-inflammatory) and M2 (anti-inflammatory), are regulated by chemokines, integrins, and other signaling molecules. Inflammatory conditions can lead to the activation of inflammasomes, which promote cytokine production and pyroptosis. Transcription factors and microRNAs (miRNAs) play essential roles in the polarization of macrophages, with miRNAs regulating gene expression at the post-transcriptional level. Metabolic reprogramming, including changes in glycolysis, fatty acid synthesis, and the tricarboxylic acid (TCA) cycle, is also involved in modulating macrophage function. Therapeutic interventions targeting monocytes and macrophages, such as blocking MIF, NLRP3, and integrins, show promise in treating inflammatory diseases. The plasticity and multifaceted roles of monocytes and macrophages make them attractive therapeutic targets, but developing effective strategies remains a challenge due to the complexity of their functions and the need for precise regulation.