Systemic sclerosis (SSc) is a highly complex disease whose heterogeneity includes multiple aspects of the condition, such as clinical presentation, progression, extent and type of organ involvement, and clinical outcomes. Thus far, these features remain not easily predictable both at the patient group level and in a given patient with regard to age at onset and clinical course. The unpredictable clinical course represents an obstacle to focusing potentially effective treatment in patients that need it the most. At the time of organ involvement and clinical diagnosis, most of the clinical manifestations are irreversible; therefore, predicting outcomes becomes crucial. This can explain the multiple attempts to identify prognostic, predictive, and monitoring-both soluble and imaging-biomarkers over the past years. They range from the currently most used biomarkers, the autoantibodies associated with disease-specific clinical features and course, to the single recently proposed skin, lung, cardiac involvement biomarkers and to the composite scores capturing multiple aspects of the disease. This review will focus on soluble and imaging biomarkers that recently showed promising evidence for outcome stratification in patients with SSc.