The millimeter-wave (mm-wave) frequency band has emerged as a means to overcome current radio frequency spectral limitations and represents an interesting solution to fulfill the bandwidth and networking requirements of fifth generation (5G) mobile communications and beyond. Photonic generation of these frequencies holds advantages over electronic methods in terms of cost and effective network distribution. Due to their coherent nature, optical frequency combs (OFC) are a promising solution for the efficient generation of mm-wave frequencies. The work outlined examines the use of OFCs in a mm-wave radio-over-fiber (RoF) heterodyne system with regard to the specific requirements of a 5G candidate waveform, universally filtered orthogonal frequency division multiplexing. Through experimentation and simulation, the key limitations of linewidth, effective path length difference, and relative intensity noise (RIN) are explored. Results are presented, in terms of error vector magnitude (EVM), for a wide range of system parameters highlighting important considerations to be taken in designing future mm-wave RoF systems employing OFCs. Performance of ∼5% EVM using single sideband modulation is achieved for optimized system conditions and an RIN level of −132 dB/Hz.