Despite advances in medical research, the burden of disease in most countries remains high.Further, health inequalities continue to grow and emerging infectious diseases are still wreaking havoc across countries. To respond to contemporary public health challenges, a new systems thinking paradigm has emerged that highlighted a holistic approach towards health systems, resulting to an emerging field -health policy and systems research (HPSR). HPSR seeks to understand and enhance how societies organize themselves in achieving collective health goals, and how different actors interact in the policy and implementation processes. However, research gaps remain particularly in applying this paradigm to strengthen health systems performance across countries. This thesis contributes to HPSR by: a. examining the underlying concepts of health systems strengthening; b. determining how health systems contribute to better health outcomes, particularly on reducing infant mortality rates and improving life expectancies at birth, and c. understanding mechanisms to use findings from health systems strengthening assessments to inform global and national-level health policymaking processes.In 2015, 40% of the Global Fund investments go toward health systems strengthening (HSS). The global health threats posed by recent viral epidemics such as Ebola and Zika even further increased calls to invest in and develop better health systems. These health systems investments were also in most cases subjected to performance-based funding, but contrary to other monitoring and evaluation methods used for other health programs, health systems monitoring and evaluation demand a new analytical frame due to its complexity, along with the very different country capacities, uneven data sources and data availability and quality, including the varied contexts that drive priority areas for health systems. As such, monitoring these initiatives remain to be highly contentious despite its importance to inform health resource allocation. In particular, studies often highlighted different conceptual and methodological challenges associated with health systems assessments worldwide.To address these issues, I first introduced a new HSS framework based on existing monitoring and evaluation frameworks collected from my field experience, systematic reviews, and thematic analyses of existing HSS documents and database. Based on the developed HSS framework, existing HSS indicators were also examined to guide further analysis. Further, I quantitatively assessed health systems performance using a new composite indicator based on previous efforts for a global health systems performance index. To do this index, I used data collected from the Demographic Health Surveys, the World Bank Indicators, and the World Health Organisation ii (WHO) Global Health Surveys. In particular, I used fixed-effects and random-effects regression analyses to determine how each health system characteristic affects health outcomes, particularly infant mortality rates and life expectan...