Despite the increased interest in economic evaluations, there are difficulties in applying the results of such studies in practice. Therefore, the “Research Agenda for Health Economic Evaluation” (RAHEE) project was initiated, which aimed to improve the use of health economic evidence in practice for the 10 highest burden conditions in the European Union (including low back pain [LBP] and neck pain [NP]). This was done by undertaking literature mapping and convening an Expert Panel meeting, during which the literature mapping results were discussed and evidence gaps and methodological constraints were identified. The current paper is a part of the RAHEE project and aimed to identify economic evidence gaps and methodological constraints in the LBP and NP literature, in particular. The literature mapping revealed that economic evidence was unavailable for various commonly used LBP and NP treatments (e.g., injections, traction, and discography). Even if economic evidence was available, many treatments were only evaluated in a single study or studies for the same intervention were highly heterogeneous in terms of their patient population, control condition, follow-up duration, setting, and/or economic perspective. Up until now, this has prevented economic evaluation results from being statistically pooled in the LBP and NP literature, and strong conclusions about the cost-effectiveness of LBP and NP treatments can therefore not be made. The Expert Panel identified the need for further high-quality economic evaluations, especially on surgery versus conservative care and competing treatment options for chronic LBP. Handling of uncertainty and reporting quality were considered the most important methodological challenges.