The need for increased clinical efficacy and efficiency has been the main force in developing artificial intelligence (AI) tools in medical imaging. The INCISIVE project is a European Union-funded initiative aiming to revolutionize cancer imaging methods using AI technology. It seeks to address limitations in imaging techniques by developing an AI-based toolbox that improves accuracy, specificity, sensitivity, interpretability, and cost-effectiveness. To ensure the successful implementation of the INCISIVE AI service, a study was conducted to understand the needs, challenges, and expectations of health care professionals (HCPs) regarding the proposed toolbox and any potential implementation barriers. A mixed methods study consisting of 2 phases was conducted. Phase 1 involved user experience (UX) design workshops with users of the INCISIVE AI toolbox. Phase 2 involved a Delphi study conducted through a series of sequential questionnaires. To recruit, a purposive sampling strategy based on the project's consortium network was used. In total, 16 HCPs from Serbia, Italy, Greece, Cyprus, Spain, and the United Kingdom participated in the UX design workshops and 12 completed the Delphi study. Descriptive statistics were performed using SPSS (IBM Corp), enabling the calculation of mean rank scores of the Delphi study's lists. The qualitative data collected via the UX design workshops was analyzed using NVivo (version 12; Lumivero) software. The workshops facilitated brainstorming and identification of the INCISIVE AI toolbox's desired features and implementation barriers. Subsequently, the Delphi study was instrumental in ranking these features, showing a strong consensus among HCPs (W=0.741, P<.001). Additionally, this study also identified implementation barriers, revealing a strong consensus among HCPs (W=0.705, P<.001). Key findings indicated that the INCISIVE AI toolbox could assist in areas such as misdiagnosis, overdiagnosis, delays in diagnosis, detection of minor lesions, decision-making in disagreement, treatment allocation, disease prognosis, prediction, treatment response prediction, and care integration throughout the patient journey. Limited resources, lack of organizational and managerial support, and data entry variability were some of the identified barriers. HCPs also had an explicit interest in AI explainability, desiring feature relevance explanations or a combination of feature relevance and visual explanations within the toolbox. The results provide a thorough examination of the INCISIVE AI toolbox's design elements as required by the end users and potential barriers to its implementation, thus guiding the design and implementation of the INCISIVE technology. The outcome offers information about the degree of AI explainability required of the INCISIVE AI toolbox across the three services: (1) initial diagnosis; (2) disease staging, differentiation, and characterization; and (3) treatment and follow-up indicated for the toolbox. By considering the perspective of end users, INCISIVE aims to develop a solution that effectively meets their needs and drives adoption.