<p>The importance of cryogenic electron tomography (cryo-ET), particularly cryogenic cellular tomography, in uncovering the complexity of eukaryotic cell systems is only beginning to be fully recognized. As the only structural technique capable of generating detailed, three-dimensional visualizations of cellular architecture in situ at sub-nanometre resolution, cryo-ET offers unmatched insights into cell biology and disease mechanisms. Integrating cryo-ET with light microscopy techniques allows researchers to localize specific regions of interest, then directly correlate them with high-resolution structural data, enabling the investigation of cellular components and dynamic processes with a level of precision previously unattainable. Despite its transformative potential, mastering integrative light microscopy techniques and cryo-ET workflows remains highly challenging. These techniques require specialized equipment, extensive hands-on experience and a deep understanding of practical nuances, many of which are acquired only through practice. In this Primer, we highlight key considerations, tips and common pitfalls to help guide newcomers to these approaches as they navigate how to begin and what challenges to anticipate.</p>