Hand syndactyly is a congenital malformation resulting from the failure of differentiation between two or more digits, resulting in a subsequent fusion. This systematic review aims to comprehensively analyze the genetic and embryological mechanisms underlying both syndromic and non-syndromic variants of hand syndactyly, as well as evaluate the effectiveness of surgical interventions utilized in the correction of this congenital anomaly to improve patient outcomes and reduce complications. The review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and systematically searched PubMed, Google Scholar, ScienceDirect, and Cochrane databases without time restrictions up to August 2024. Studies included in this review examined (1) genetic and embryological mechanisms of syndactyly; (2) classification systems; and (3) surgical treatment outcomes. Reference lists of identified articles were manually screened for additional studies. Exclusion criteria included (1) conference papers, letters to the editor, reviews, and video articles; (2) studies on congenital hand malformations other than syndactyly; (3) studies involving animal subjects; (4) studies with updated reviews from the same authors; (5) preliminary studies; and (6) studies with duplicate information. Out of 3015 initial records and 212 additional sources, 88 studies met the inclusion criteria, providing insights into the genetics, embryology, and surgical management of hand syndactyly. Risk of bias was assessed using the traffic light plot within the Robvis risk-of-bias framework. While many studies demonstrated methodological rigor based on the key domains assessed, limitations included recall bias in retrospective cohort studies, inconsistent stratification of surgical outcomes, and inadequate control for confounding factors. The findings emphasize the importance of early diagnosis and intervention, particularly surgical correction between 18 and 24 months, to improve functional and aesthetic outcomes. Various surgical techniques have been explored, each with distinct benefits depending on the type and extent of malformation. Patient-reported outcomes show higher satisfaction with upper extremity function and reduced pain interference, highlighting the value of personalized treatment approaches. Despite expanded classification systems and improved surgical techniques, the multifactorial etiology of hand syndactyly requires further investigation to refine diagnostic strategies and enhance treatment protocols, ultimately improving patient care.