As current practice in majors and independents alike, an artificial lift optimization strategy over a horizontal well's life will include selection (what to use), asset management (when and where), surveillance (what is happening) and measurement (how effective). The essential artificial lift question being asked in this common optimization framework is to determine whether knowledge can be gained by case studies experience of how different equipment and operating conditions can change the flowing multiphase mixture towards required goals, e.g. to cause liquids lift, to reduce interfacial tension, to drop hydrostatic pressure gradient. In this paper, we showcase the importance of including predictive modeling (why is it happening) and proactive analysis and design (how to improve and minimize cost) to an artificial lift optimization strategy using the latest commercial multiphase flow simulation tool, PipeFractionalFlow™. Four actual case histories, one Permian, one Wolfcamp and two Western Canadian Sedimentary Basin (WCSB) horizontal wells, are analyzed from this new artificial lift simulation perspective for common types of horizontal well artificial lift needs. In particular, the impact of an as-drilled Wolfcamp horizontal well trajectory and a toe-up and toe-down variant of this trajectory is connected via simulation to the differences in the late life well predictions during gas lift operations. Additionally, for the first time, the measured improvements in horizontal well artificial lift performance of the HEAL System™ are understood and quantified using physics-based simulation. The Horizontal Enhanced Artificial Lift, or HEAL System, as installed in two horizontal wells in the WCSB are modeled in PipeFractionalFlow (one well in low-data-frequency, steady-state, daily-averaged flow mode and another well in high-data-frequency, transient, real-time flow mode), in which surface-to-downhole wellbore multiphase flow behavior and slugging characteristics both before and after the HEAL System installation are accurately simulated. The overall objective of this work is to highlight how reliable multiphase flow analytical modeling capability can help to better understand wellbore multiphase flowing mixture behavior under horizontal well artificial lift operating conditions across a well's life.