Eye tracking and other behavioral measurements collected from patient-participants in their hospital rooms afford a unique opportunity to study immersive natural behavior for basic and clinical-translational research, and also requires addressing important logistical, technical, and ethical challenges. Hospital rooms provide the opportunity to richly capture both clinically relevant and ordinary natural behavior. As clinical settings, they add the potential to study the relationship between behavior and physiology by collecting physiological data synchronized to behavioral measures from participants. Combining eye-tracking, other behavioral measures, and physiological measurements enables clinical-translational research into understanding the participants' disorders and clinician-patient interactions, as well as basic research into natural, real world behavior as participants eat, read, converse with friends and family, etc. Here we describe a paradigm in individuals undergoing surgical treatment for epilepsy who spend 1-2 weeks in the hospital with electrodes implanted in their brain to determine the source of their seizures. This provides the unique opportunity to record behavior using eye tracking glasses customized to address clinically-related ergonomic concerns, synchronized direct neural recordings, use computer vision to assist with video annotation, and apply multivariate machine learning analyses to multimodal data encompassing hours of natural behavior. We discuss the acquisition, quality control, annotation, and analysis pipelines to study the neural basis of real world social and affective perception during natural conversations with friends and family in participants with epilepsy. We also discuss clinical, logistical, and ethical and privacy considerations that must be addressed to acquire high quality multimodal data in this setting.