Background The principle of HRM requires employees to come up with novelty and creative ideas in work organizations. Prior research viewed high-performance work systems (HPWS) as an essential factor that promotes innovation and performance outcomes as it encourages employee creativity, risk-taking, and experimentation.Objective The current study investigated the influence of HPWS on innovative work behavior in medium-sized manufacturing enterprises through work engagement. Although much has been done to analyze various outcomes of high-performance work systems in large-scale manufacturing industries, little is known about its implementation amongst medium-sized manufacturing enterprises in Malaysia.Methods This study employed a group of 170 middle-management employees from medium-sized manufacturing businesses in Klang Valley, Malaysia. To perform the analysis, the researchers used SmartPLS 3.0 software. The list of medium-sized enterprises in the Klang Valley area was obtained from SME Corporation Malaysia. G*Power version 3.1.9.2 statistical program was used to perform power analysis in determining the minimum sample size for this study. The theory of job demands-resources (JD-R) model underpins the linkages between HPWS and IWB of employees in medium-sized manufacturing enterprises.Results The outcome indicated a noteworthy relationship between innovative work behavior and selective staffing, mentoring, and employee participation. Additionally, the study demonstrated that work engagement is crucial in promoting innovative work behavior with a medium effect size. Moreover, the connection between selective staffing, mentoring, and employee participation is mediated by work engagement.Conclusions This research expands the existing information on ways to implement HPWS in medium-sized manufacturing companies. Moreover, it offers practical guidance to decision-makers, especially in promoting innovation among staff through effective high-performance work practices.