Acne vulgaris is a skin condition characterized by the inflammation or hyperactivity of sebaceous glands on the skin, which results in the creation of comedones, lesions, nodules, and perifollicular hyperkeratinization. Increased sebum production, follicular blockage, and bacterial colonization may contribute to the disease etiology. Environmental factors, hormonal imbalance, and genetic predisposition can alter the severity of the disease. Its mental and monetary effects can be problematic for the society. In this study, we examined the role of isotretinoin in the treatment of acne vulgaris based on evidence from prior research. This review literature study compiled publications on the treatment of acne vulgaris from 1985 to 2022 based on PubMed and Google Scholar publications. Additional bioinformatics analyses were accompanied by GeneCards, STRING model, and DrugBank databases. These complementary analyses were designed to obtain a better perspective of personalized medicine which is highly required for dose-precise administrations of acne vulgaris treatment. Isotretinoin has been recognized as an effective treatment for acne vulgaris, particularly in cases that have been resistant to previous medications or have resulted in scarring, according to gathered data. Oral isotretinoin inhibits the proliferation of Propionibacterium acne, a critical factor in the development of acne lesions; also, it has been shown to be effective in reducing the number of Propionibacterium-resistant patients and regulating sebum production and reducing sebaceous gland size more effectively than other treatment options resulting in general improvements in skin clarity and acne severity and reduce inflammatory in 90% of patients. In addition to its efficacy, the majority of patients have shown that oral isotretinoin is well tolerated. This review highlights the use of oral retinoids, particularly isotretinoin, as an effective and well-tolerated treatment option for acne vulgaris. It has been proven that oral isotretinoin is useful for achieving long-lasting remission in patients with severe or resistant instances. Despite the fact that oral isotretinoin is related to a number of potential harmful effects, skin dryness was the most common side effect reported by patients that can be managed with the aid of suitable monitoring and drug administration against specific genes identified by genotyping of the susceptible variants of genes involved in TGFβ signaling pathway.