Patients with comorbid mental health and chronic conditions often receive care from both psychiatrists and primary care physicians (PCPs). The introduction of multiple providers into the care process introduces opportunities for disruptions in care continuity. The purpose of this study was to explore psychiatrists' and PCPs' comfort prescribing, along with their comfort having other physician specialties prescribe medications for cardiometabolic, psychiatric, and neurological/behavioral conditions. This cross-sectional study utilized an online, validated, pilot-tested, anonymous survey to examine prescribing practices of psychiatrists and PCPs. Eligible participants included physicians with medical degrees, U.S. prescribing authority, and active patient care for ≥2 days/week. Outcomes of interest were physicians' self-comfort and cross-specialty comfort (other specialists prescribing mutual patients' medications) prescribing cardiometabolic, psychiatric, and neurological/behavioral medications. Comfort prescribing was measured using 7-point Likert scales. Discrepancies in comfort were analyzed using student's, one-sample, and paired t-tests. Multiple linear regressions examined associations between physician practice characteristics and physicians' comfort-level prescribing cardiometabolic and psychiatric medication categories. Among 50 psychiatrists and 50 PCPs, psychiatrists reported significantly lower self-comfort prescribing cardiometabolic medications (mean ± SD = 2.99 ± 1.63 vs. 6.77 ± 0.39, p < 0.001), but significantly higher self-comfort prescribing psychiatric medications (mean ± SD = 6.79 ± 0.41 vs. 6.00 ± 0.88, p < 0.001) and neurological/behavioral medications (mean ± SD = 6.48 ± 0.74 vs. 5.56 ± 1.68, p < 0.001) than PCPs. After adjusting for covariates, physician specialty was strongly associated with self-comfort prescribing cardiometabolic and psychiatric medication categories (both p < 0.001). Differences between self-comfort and cross-specialty comfort were identified. Because comfort prescribing medications differed by physician type, incorporating psychiatrists through collaborative methods with PCPs could potentially ensure comfort among physicians when initiating medications.