Inclusion Criteria:
* Male \>=18 years old.
* Able to provide written informed consent and comply with the study procedures.
* Participants with advanced and/or metastatic histologically or cytologically confirmed adenocarcinoma of the prostate without small cell histology or neuroendocrine transformation.
* Serum testosterone levels less than or equal to (\<=) 0.5 nanograms per millilitre (ng/mL) (\<=1.73 nanomoles per litre \[nmol/L\]) at screening if on an androgen receptor prostate inhibitor in combination with Androgen Deprivation Therapy (ADT).
* Progression (as defined below) after the receipt of at least one or more approved second-generation androgen-receptor-pathway inhibitors with or without a prior course of taxane therapy, as long as the subject has not received more than three lines of therapy in the CRPC setting. If a subject is known positive for any of the specific gene mutations of BRCA1/2, PALB2, or HRD and chose not to receive an approved PARP-inhibitor they are eligible for the study. Documented progressive disease at screening as assessed by the Investigator with at least one of the following criteria:
* Serum/plasma PSA progression defined as 2 consecutive increases in PSA over a previous reference value measured at least 1 week apart. 1.0 ng/mL is the minimal starting value if confirmed rise is only indication of progression.
* Radiographic disease progression in soft tissue based on response evaluation criteria in solid tumors (RECIST) v1.1 criteria with or without PSA progression as per prostate cancer working group 3 (PCWG3).
* Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on a bone scan as per PCWG3 with or without PSA progression.
* Able to undergo general anesthesia, MAC anesthesia, or conscious sedation.
* Eastern Cooperative Oncology Group (ECOG) performance status of less than (\<) 2.
* Life expectancy \>=6 months
* Last dose of previous anticancer therapy (excluding hormonal therapy) must by 28 days prior to first study treatment. For subjects who previously received lutetium Lu 177 vipivotide tetraxetan (Pluvicto®), the last dose must have been administered \> 90 days prior to first study treatment. Subjects may remain on ADT and/or androgen receptor pathway inhibitor at time of study entry, per Investigator discretion.
* Resolution of all acute toxic effects (excluding alopecia) of any prior anticancer therapy.
* For males with female partners of childbearing potential, even if surgically sterilized (that is \[i.e.\], status post vasectomy), who agree to practice:
1. effective barrier contraception during the treatment period and through 120-150 days after last dose, OR
2. true abstinence, when this is in line with the preferred and usual lifestyle of the participants. Periodic abstinence (for example \[e.g.\], calendar, ovulation, symptothermal, post ovulation methods), withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.
* Must have at least one measurable lesion per RECIST v1.1 at time of screening.
* Must have at least one lesion suitable for SYNC-T Therapy identified by radiographic imaging as defined below:
* Soft tissue lesion (e.g., prostate, lung) must be at least 1 cm in at least two dimensions.
* Lymph node lesion of at least 1.5 cm (short axis) or 1.0 cm if positive per PET scan.
* Exophytic component of a bone lesion that is measurable per RECIST v1.1. Soft tissue and lymph nodes must be demonstrable on CT/MRI and accessible either transperineally or percutaneously to permit tumor biopsy, cryolysis, and immunotherapy infusion.
The eligible tumor lesion for intratumoral infusion cannot be a tumor that is adjacent to vital structures such as major nerves or blood vessels or at risk of airway compromise in the event of post-infusion tumor swelling/inflammation.
* Participants receiving bone resorptive therapy must be on stable doses for at least 42 days prior to the oncolysis.
* In the opinion of the Investigator, there is no other meaningful life prolonging therapy option available, or the participant refuses other therapy, outside of anti-hormonal therapy.
* Adequate bone marrow, renal, and hepatic function.
* Participants agrees to provide tumor tissue and undergo an on-treatment tumor biopsy.
Exclusion Criteria:
* Has a known other primary malignancy other than prostate cancer that is progressing or has required active treatment in the last 3 years, excluding basal and squamous cell carcinoma, papillary thyroid cancer, and ductal carcinoma in situ of the breast.
* Has an obstructed urinary system before or after stenting.
* Has undergone major surgery, including local prostate intervention (excluding prostate biopsy), within 28 days prior to the first dose of study treatment and has not recovered adequately from the toxicities and/or complications.
* Has used any anticoagulants or other blood thinners pre-study treatments within the protocol-defined timelines.
* Has an active infection (including tuberculosis) requiring systemic therapy.
* Has a history of non-infectious pneumonitis that requires steroids.
* Has received a live vaccine within 30 days prior to the planned first study treatment.
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 28 days prior to the first study treatment.
* Significant cardiac or other medical illness such as severe congestive heart failure, unstable angina, or serious cardiac arrhythmia (e.g., New York Heart Association Class 4), or history of previous heart failure.
* Fridericia corrected QT interval (QTcF) greater than (\>) 470 millisecond (msec) (men) on a 12-lead electrocardiogram (ECG) during the screening period.
* Malignant pleural effusions or ascites that require immediate intervention.
* Brain metastases (includes history of).
* Immunocompromised status due to:
* Active autoimmune diseases such as Addison's disease, Hashimoto's thyroiditis, systemic lupus erythematosus, Sjogren syndrome, scleroderma, myasthenia gravis, Goodpasture syndrome or active Grave's disease. Participants with a history of autoimmunity that has not required systemic immunosuppressive therapy or does not threaten vital organ function including CNS, heart, lungs, kidneys, skin, and GI tract will be allowed.
* Other immunodeficiency diseases that in the opinion of the Investigator, with consultation with Medical Monitor, could compromise the participant or limit treatment efficacy.
* Uncontrolled or unmanaged diabetes, hypersensitivity, or other illness or disease that in the opinion of the Investigator, with consultation with Medical Monitor (MM), makes the subject a poor candidate.
* History of bone marrow/stem cell transplant.
* Participants having human immunodeficiency virus (HIV) infection or acquired immune deficiency syndrome (AIDS) are not eligible for enrollment.
* Active coronavirus disease-2019 (COVID-19) infection or tests positive for COVID-19 a day before or the day of planned study treatment.
* Participants who have active viral (any etiology) hepatitis are excluded.
* Participants with serologic evidence of chronic hepatitis B virus (HBV) infection (defined by a positive hepatitis B surface antigen \[HBsAg\] test and a positive hepatitis B core antibody (anti-HBc) test) who have a viral load below the limit quantification (HBV deoxyribonucleic acid \[DNA\] titer \<1000 copies per milliliters \[cps/mL\] or 200 international units per milliliter \[IU/mL\]) and are not currently on viral suppressive therapy may be eligible and should be discussed with the Sponsor's Medical Monitor.
* Participants with a history of hepatitis C virus (HCV) infection should have completed curative antiviral treatment and have a viral load below the limit of quantification are eligible for study entry. Known or suspected hepatitis C infection which has not been treated and cured are not eligible. Known or suspected hepatitis C currently on treatment with an undetectable viral load are eligible. Patients with a history of hepatitis C virus (HCV) infection should have completed curative antiviral treatment and have a viral load below the limit of quantification are eligible for study entry.
* Participants with complications or contraindications related to the liver, including intrahepatic biliary ductal dilation, uncorrectable bleeding diathesis, and decompensated liver failure.
* Breast cancer gene (BRCA) mutation testing will be required for participants not previously treated with a PARP inhibitor, unless BRCA status is established prior to screening. If PARP-positive and participants agree to PARP therapy, they will be ineligible.
* Any condition(s) that, in the opinion of the Investigator, would increase the risk for toxicities from study treatment, or interfere with participants compliance or conduct of this study.
* Known visceral metastases, except for lung metastases.
* Known substance abuse or medical, psychological, or social conditions that may interfere with patient's participation.
* Participants who have received both chemotherapy and lutetium Lu 177 vipivotide tetraxetan (Pluvicto) in the CRPC setting.
