Compassion in healthcare provides measurable benefits to patients, physicians, and healthcare systems. However, data regarding the factors that predict care (and a lack of care) are scattered. This study systematically reviews biomedical literature within the Transactional Model of Physician Compassion and synthesizes evidence regarding the predictors of physician empathy, compassion, and related constructs (ECRC). A systematic literature search was conducted in CENTRAL, MEDLINE, PsycINFO, EMBASE, CINAHL, AMED, OvidJournals, ProQuest, Web of Science, and Scopus using search terms relating to ECRC and its predictors. Eligible studies included physicians as participants. Methodological quality was assessed based on the Cochrane Handbook, using ROBINS-I risk of bias tool for quantitative and CASP for qualitative studies. Confidence in findings was evaluated according to GRADE-CERQual approach. One hundred fifty-two included studies (74,866 physicians) highlighted the diversity of influences on compassion in healthcare (54 unique predictors). Physician-related predictors (88%) were gender, experience, values, emotions and coping strategies, quality of life, and burnout. Environmental predictors (38%) were organizational structure, resources, culture, and clinical environment and processes. Patient-related predictors (24%) were communication ease, and physicians' perceptions of patients' motives; compassion was also less forthcoming with lower SES and minority patients. Evidence related to clinical predictors (15%) was scarce; high acuity presentations predicted greater ECRC. The growth of evidence in the recent years reflects ECRC's ongoing importance. However, evidence remains scattered, concentrates on physicians' factors that may not be amenable to interventions, lacks designs permitting causal commentary, and is limited by self-reported outcomes. Inconsistent findings in the direction of the predictors' effects indicate the need to study the relationships among predictors to better understand the mechanisms of ECRCs. The current review can guide future research and interventions.