Health systems strengthening (HSS) is firmly on the global health and development agenda. While a growing evidence base seeks to understand the effectiveness of HSS, there is limited evidence regarding cost and cost-effectiveness. Without such evidence, it is hard to argue that HSS represents value for money and the level of investment needed cannot be quantified. This paper seeks to review the literature regarding the economic evaluation of HSS from low- and middle-income country (LMIC) settings, and to contribute towards the development of methods for the economic evaluation of HSS. A systematic search for literature was conducted in PubMed, Scopus and the Health Systems Evidence database. MeSH terms related to economic evaluation were combined with key words related to the concept of HSS. Of the 204 records retrieved, 52 were retained for full text review and 33 were included. Of these, 67% were published between January 2015 and June 2019. While many HSS interventions have system wide impacts, most studies (71%) investigated these impacts using a disease-specific lens (e.g. the impact of quality of care improvements on uptake of facility deliveries). HSS investments were categorized, with the majority being investments in platform efficiency (e.g. quality of care), followed by simultaneous investment in platform efficiency and platform capacity (e.g. quality of care and task shifting). This review identified a growing body of work seeking to undertake and/or conceptualize the economic evaluation of HSS in low- and middle-income countries. The majority assess HSS interventions using a disease-specific or programmatic lens, treating HSS in a similar manner to the economic evaluation of medicines and diagnostics. While this approach misses potential economies of scope from HSS investments, it allows for a preliminary understanding of relative value for money. Future research is needed to complement the emerging evidence base.