When making funding decisions, research organisations largely consider the merits (e.g. scientific rigour and feasibility) of submitted research proposals; yet, there is often little or no reference to their value for money. This may be attributed to the challenges of assessing and integrating value of research into existing research prioritisation processes. We propose a framework that considers both the merits of research and its value for money to guide health research funding decisions. A practical framework is developed based on current processes followed by funding organizations for assessing investigator-initiated research proposals, and analytical methods for evaluating the expected value of research. We apply the analytical methods to estimate the expected return on investment of two real-world grant applications. The framework comprises four sequential steps: (1) initial screening of applications for eligibility and completeness; (2) merit assessment of eligible proposals; (3) estimating the expected value of research for the shortlisted proposals that pass the first two steps and ranking of proposals based on return on investment; and (4) selecting research proposals for funding. We demonstrate how the expected value for money can be efficiently estimated using certain information provided in funding applications. The proposed framework integrates value-for-money assessment into the existing research prioritisation processes. Considering value for money to inform research funding decisions is vital to achieve efficient utilisation of research budgets and maximise returns on research investments.