The purpose of this research is to examine the underlying mechanisms inside the so-called black box that relate high performance work systems (HPWS) with employees’ well-being and job performance in hospitality. We surveyed a sample of 494 hotel workers to test a research model that related the following variables: HPWS, organizational commitment, motivation, job satisfaction, quality of life (QoL), and individual job performance. Structural equation modelling, namely through PLS-SEM, was conducted. We confirmed that HPWS directly influence employees’ motivation, organizational commitment, job satisfaction, and QoL. Additionally, workers’ motivation and organizational commitment positively influence job satisfaction, which, in turn, enhances workers’ QoL. Moreover, job satisfaction and quality of life significantly predicted individual job performance. This study contributes to unlocking the so-called black box relating HPWS with job outcomes as well as to the growing body of research that relates employees’ well-being with performance. From a managerial point of view, hospitality firms should prioritize investment in HPWS, as its design and implementation affects employees’ attitudes and behaviors. Future lines of research should consider bundles of practices instead of the whole HPWS effects on employees’ attitudes and behaviors.