Context. Psychosocial behavioral interventions (PBIs) that target patients with cancer and their caregivers face challenges in participant enrollment and retention. Objectives. 1) Describe characteristics of the patient-caregiver PBI studies; 2) examine participant enrollment and retention rates; 3) identify factors influencing participant enrollment and retention rates; and 4) explore the strategies to promote enrollment and retention rates. Methods. We identified randomized controlled trials that tested PBIs among adult patients with cancer and caregivers in five electronic databases. We conducted narrative and quantitative analyses to synthesize our findings. Results. Among 55 qualified studies reviewed, most tested the efficacy of PBIs (n = 42) and used two study arms (n = 48). Inperson meeting was the most common PBI delivery mode. The primary outcomes included quality of life, physical health, and symptoms. The average of enrollment rates of patient-caregiver dyads was 33% across studies (range 8%−100%; median = 23%). The average retention rate at the end of follow-ups was 69% (range 16%−100%; median = 70%). The number of study arms, recruitment method, type of patient-caregiver relationship, and intervention duration influenced enrollment rates. Study design (efficacy vs. pilot), follow-up duration, mode of delivery, type of relationship, and intervention duration influenced retention rates. Sixteen studies reported retention strategies, including providing money/gift cards upon study completion and/or after follow-up survey, and excluding patients with advanced cancer. Conclusion. Researchers need to incorporate effective strategies to optimize enrollment and retention in patient-caregiver PBI trials. Researchers need to report detailed study processes and PBI information to improve research transparency and increase consistency. J Pain Symptom Manage 2021;62:e279−e304. © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.