Serial homicide investigations represent one of the most complex and high-stakes domains of criminal justice. While designed to protect the public from repeat offenders, these investigations are uniquely vulnerable to systemic error. This chapter critically examines how behavioral ambiguity, investigative tunnel vision, racial bias, and procedural misconduct intersect to produce wrongful convictions in serial homicide cases. Drawing on empirical data from wrongful conviction research, the chapter explores how early behavioral inconsistencies, misapplied linkage models, and relational misattribution can derail investigations. These vulnerabilities are compounded by coercive interrogation practices, forensic misinterpretation, and structural inequities that disproportionately harm marginalized defendants. Case references, such as the wrongful conviction of Jeffrey Deskovic, illustrate how these failures unfold in real-world contexts. The chapter concludes with a set of actionable reforms, including dynamic behavioral analysis training, standardized forensic testing protocols, enhanced eyewitness procedures, and independent oversight mechanisms. These interventions are essential not only to reduce wrongful convictions but also to ensure that serial crime investigations uphold the principles of accuracy, accountability, and justice.