Ovarian cancer ranks among the deadliest forms of gynecological malignancies, presenting significant challenges in early detection, offering grim prognosis, and carrying high rates of recurrence and mortality. This malignancy comprises a variety of subtypes, each characterized by differences in molecular traits and clinical behavior. Among these subtypes is ovarian serous carcinoma (OSC), which encompasses both high-grade serous ovarian carcinoma (HGSOC) and low-grade serous ovarian carcinoma (LGSOC). OSC is marked by genomic instability, resulting in the malfunction of tumor suppressor genes and oncogenes due to factors like homologous recombination deficiency (HRD), copy number variations (CNV), chromosomal abnormalities, and epigenetic changes. LGSOC is distinguished by overexpression in genes such as KRAS, NRAS, BRAF mutations, and PTEN inactivation mutations. In contrast, HGSOC is characterized by mutations in TP53, BRCA1 and BRCA2, NF1, PB1, CDK12, and the amplification of oncogenes like CCNE1, NOTCH3, MYC, MECOM, and P16 expression. The pursuit of understanding and targeting genomic instability has significantly influenced approaches to screening, prognosis, and therapeutic strategies in OSC. Further insights from molecular investigations have unveiled the regulatory role of microRNAs (short non-coding RNAs) in modulating the expression of target tumor suppressors and oncogenes by interacting with messenger RNA (mRNA), thus regulating gene expression in OSCs. This review emphasizes the importance of differentially expressed genes and miRNAs in the initiation and progression of OSC, suggesting the potential utility of miRNA-based therapies for this malignancy. Therefore, for effective screening, diagnosis, and personalized therapy, a thorough examination of miRNA expression alterations is implicated in both HGSOC and LGSOC. This review aims to provide a comprehensive understanding of microRNA signatures linked to genomic instability in both HGSOC and LGSOC, focusing on how genomic instability, intertwined with tumor suppressor genes, oncogenes, and miRNA alterations, correlates between these two subtypes of ovarian cancer.