The goal of this study is to assess the safety, tolerability and immunogenicity of mRNA-1769 in healthy adult participants.

Inclusion Criteria:

• Has a body mass index (BMI) between ≥18 kilogram per square meter (kg/m^2) to ≤39 kg/m^2.
• For female participants of childbearing potential: must have a negative highly sensitive pregnancy test with 28 days before the first dose of study drug, uses approved contraception during the study intervention period and for at least 3 months after the last dose of study drug, and not currently breastfeeding.

Exclusion Criteria:

• History of smallpox vaccination, vaccination with any poxvirus-based vaccine, history of of/or recent exposure to Mpox (MPX) (defined as close contact with a confirmed case of MPX within the past 14 days).
• Participant should not have any significant, progressive, unstable, or uncontrolled clinical condition, including any condition that may affect participant safety, assessment of safety endpoints, assessment of immune response, or adherence to study procedures per Investigator judgement.
• Participant is undergoing investigations for a potential chronic medical disorder.
• Bleeding disorder considered a contraindication to IM injection or phlebotomy.
• Dermatologic conditions that could affect local solicited AR assessments.
• History of anaphylactic reaction or allergic reactions that required medical intervention following any vaccine.
• Known or suspected allergy to any component of mRNA-1769.
• History of malignancy within previous 10 years (excluding non-melanoma skin cancer).
• Participant has any medical, psychiatric, or occupational condition, including reported history of drug or alcohol abuse, that, in the opinion of the Investigator, might pose additional risk due to participation in the study or could interfere with the interpretation of study results.
• Participant has received systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to Screening (for corticosteroids, ≥10 mg/day of prednisone or equivalent) or is anticipating the need for immunosuppressive treatment at any time during participation in the study. Topical tacrolimus is allowed if not used within 14 days prior to the day of enrolment. Participants may be rescheduled for enrolment if they no longer meet this criterion within the Screening Period. Inhaled, nasal, and topical steroids are allowed.
• Receipt or planned receipt of: Any vaccine(s), authorised or approved by local health agency, including mRNA vaccine, ≤28 days prior to the first injection through 28 days after the last dose of investigational (IMP).
• Intravenous blood products (red cells, platelets, immunoglobulins) within 3 months prior to the first injection up to the end of the study.
• Participated in an interventional study/received an investigational product within 28 days prior to the Screening Period or plans to do so while enroled in this study.

Note: Other inclusion and exclusion criteria may apply.